Novel substituted condensed ring compound

ABSTRACT

The present invention provides a novel compound having an excellent β-lactamase inhibitory effect. The present invention provides: a compound which has an excellent β-lactamase inhibitory effect, and is represented by formula (1a), (1b) or (11); or a pharmaceutically acceptable salt thereof. This compound provides a prophylactic or therapeutic agent effective for bacterial infections when used in combination with β-lactam-based drugs or used as a single agent. The present invention also provides a prophylactic or therapeutic agent effective for treating various diseases, by being used in combination with β-lactam-based drugs.

TECHNICAL FIELD

The present invention relates to a substituted condensed compound that is useful as a medicament or a pharmaceutically acceptable salt thereof. More specifically, the present invention relates to a pharmaceutical composition comprising a novel substituted condensed ring compound or a pharmaceutically acceptable salt thereof, or a medicament comprising the substituted condensed ring compound or a pharmaceutically acceptable salt thereof (therapeutic agent, prophylactic agent, etc.).

BACKGROUND ART

Since the discovery of penicillin, antimicrobial agents have taken an important role in the treatment of infections.

In particular, β-lactam agents (e.g., penicillin antimicrobial agents, cephalosporin antimicrobial agents, and carbapenem antimicrobial agents) are agents that are most commonly used in the treatment of bacterial infections in view of their potent sterilizing capacity and high degree of safety. However, with increased use of β-lactam agents, emergence and prevalence of pathogenic bacteria that have acquired resistance to β-lactam agents have become a global problem. Examples of the mechanism of acquiring resistance of such pathogens include production of β-lactamase, structural change in the target molecule of a β-lactam agent, reduced drug permeation into microbial cells, elevated drug discharge, and the like. In particular, production of β-lactamase, which degrades and inactivates β-lactam agents, is one of the most influential in the maintenance of efficacy of β-lactam agents. Various bacteria are involved in the evolution of β-lactamase that antagonizes the efficacy of various β-lactam agents. β-lactamases can be classified into 4 classes based on their amino acid sequences, i.e., Ambler classes A, B, C, and D. Since class A, C, and D enzymes have a serine residue at the center of enzymatic activity, they are known as serine-β-lactamases. Since class B enzymes do not have a serine residue at the center of enzymatic activity but have zinc metal ion (Zn²⁺), they are known as metallo-β-lactamases (zinc-β-lactamases).

It has been already confirmed that concomitant use of an agent for inhibiting β-lactamase and a β-lactam agent is effective for solving the problem of resistance acquisition due to production of β-lactamase. It is known that commercially available agents for inhibiting β-lactamase, clavulanic acid, sulbactam, and tazobactam primarily inhibit class A β-lactamases excluding KPC (Klebsiella pneumoniae Carbapenemase), and avibactam inhibits class A β-lactamases (including KPC), class C β-lactamases, and some class D β-lactamases including OXA-48 (Non Patent Literature 1). However, these existing agents for inhibiting β-lactamase cannot effectively and broadly inhibit all β-lactamases produced by various bacteria. For example, such inhibiting agents do not exert an effect on class B metallo-β lactamases. Recently, β-lactamases called ESBLs (Extended Spectrum β-Lactamases) that can degrade more substrates (β-lactam agent) compared to conventional β-lactamases were isolated, which have led to a problem as a new resistant bacteria, especially as a causative bacteria for hospital-acquired infections in the US and Europe. In addition, emergence and prevalence of metallo-β-lactamase producing bacteria is becoming a problem in Japan. In view of such a circumstance, it is very important to address β-lactamase producing bacteria including ESBLs and metallo-β-lactamase for the prophylaxis of hospital-acquired infections. Furthermore, pathogenic bacteria evolve quickly, such that emergence of new β-lactamase resistant bacteria is very likely. Accordingly, as a solution to such problems or as a safeguard against such issues to be addressed, there is a demand for the development of a novel agent for inhibiting β-lactamase that has a different structure from existing agents for inhibiting β-lactamase, whereby a broader β-lactamase inhibitory action or metallo-β-lactamase inhibitory action is expected.

Recently, boronic acid derivatives with β-lactamase inhibitory action have been reported in Patent Literatures 1 to 13 and the like. Patent Literature 10 discloses a structure formed by fusing a saturated cycloalkyl ring or the like to a ring comprising boronic acid. These Patent Literatures do not disclose a structure related to the novel substituted condensed ring compounds encompassed by the present invention, i.e., a boronic acid compound group having a non-aryl heterocycle (preferably a nitrogen-containing non-aryl heterocycle, and more preferably an azetidine ring) structure having a specific substitution mode on a side chain at a specific position (wherein the specific substitution mode is, for example, a mode having a specific substitution on the non-aryl heterocycle via an alkylene group or a mode having a specific substituent on the non-aryl heterocycle via an oxo substituent (—C(═O)—, —S(═O)—, —S(═O)₂—, or the like) and a structure formed by fusing a cyclopropane ring to a ring comprising boronic acid as a combination.

CITATION LIST Patent Literature

-   [PTL 1] WO 2014/107535 -   [PTL 2] WO 2014/107536 -   [PTL 3] WO 2015/179308 -   [PTL 4] WO 2016/003929 -   [PTL 5] WO 2016/149393 -   [PTL 6] WO 2014/089365 -   [PTL 7] WO 2014/110442 -   [PTL 8] WO 2014/151958 -   [PTL 9] WO 2015/191907 -   [PTL 10] WO 2018/005662 -   [PTL 11] WO 2018/199291 -   [PTL 12] WO 2019/009369 -   [PTL 13] WO 2019/009370

Non Patent Literature

-   [NPL 1] Buynak. J D. Expert Opinion on Therapeutic Patents, 2013,     23(11), 1469-1481.

SUMMARY OF INVENTION Solution to Problem

The present invention provides a novel compound having excellent β-lactamase inhibitory action and provides a prophylactic or therapeutic agent that is useful for a bacterial infection, alone or in concomitant use with a β-lactam agent. Specifically, the present invention provides a prophylactic or therapeutic agent that is useful for therapy, by concomitant use with a β-lactam agent, of a disease such as sepsis, febrile neutropenia, bacterial meningitis, bacterial endocarditis, otitis media, sinusitis, pneumonia, lung abscess, empyema, secondary infection of a chronic respiratory disease, pharyngolaryngitis, tonsillitis, osteomyelitis, arthritis, peritonitis, intraperitoneal abscess, cholecystitis, cholangitis, liver abscess, deep skin infection, lymphangitis/lymphadenitis, secondary infection of trauma, burn injury, surgical wound, or the like, urinary tract infection, genital infection, eye infection, or odontogenic infection.

More specifically, the inventors completed the present invention by finding that a compound represented by formula (1a), (1b), or (11) described below or a pharmaceutically acceptable salt thereof (also referred to as the “compound of the invention” hereinafter) has excellent β-lactamase inhibitory action.

Specifically, the present invention is the following.

[Item 1]

A compound represented by formula (1a) or (1b):

or a pharmaceutically acceptable salt thereof wherein

G is an oxygen atom, a sulfur atom, or —NR^(a1)—,

X is a hydroxyl group, an optionally substituted alkoxy group, or —NR^(a2)R^(b1),

R^(a1), R^(a2), and R^(b1) are the same or different, each independently a hydrogen atom, a hydroxyl group, an optionally substituted hydrocarbyl group, or an optionally substituted heterohydrocarbyl group,

wherein R^(a2) and R^(b1) together may form an optionally substituted nitrogen-containing non-aryl heterocycle,

L¹ is a single bond, an oxygen atom, a sulfur atom, —SO—, —SO₂—, an optionally substituted hydrocarbylene group, or an optionally substituted heterohydrocarbylene group,

L² is a single bond or an optionally substituted hydrocarbylene group,

Z is a hydrogen atom, a hydroxyl group, an optionally substituted hydrocarbyl group, or an optionally substituted heterohydrocarbyl group,

one of R¹, R², and R³ is represented by formula (2):

wherein

Y is an oxygen atom, a sulfur atom, or —NR^(j)—, and R^(j) is a hydrogen atom, a hydroxyl group, or an optionally substituted hydrocarbyl group,

ring A is an optionally substituted non-aryl heterocycle,

L³ is an oxygen atom, a sulfur atom, an optionally substituted hydrocarbylene group, an optionally substituted heterohydrocarbylene group, optionally substituted —NH—, optionally substituted —NH—SO₂—, —S(═O)—, or —S(═O)₂—,

L⁴ is a single bond, an optionally substituted hydrocarbylene group, an optionally substituted heterohydrocarbylene group, or —C(═N—OR^(h1))—,

R^(h1) is

1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₁₀ alicyclic group, 4) C₆₋₁₀ aryl, 5) 5- or 6-membered heteroaryl, or 6) a 4- to 10-membered non-aryl heterocycle, (wherein each substituent from 2) to 6) is optionally substituted),

R⁵ is a hydrogen atom, a hydroxyl group, an optionally substituted hydrocarbyl group, an optionally substituted heterohydrocarbyl group, optionally substituted —NHOH, a sulfo group (sulfonic acid group), optionally substituted —SO₂H, optionally substituted —SO₂—NH₂, optionally substituted —S(═O)(═NH)H, optionally substituted —NH—SO₂—H, optionally substituted —NH—SO₂—NH₂, optionally substituted —N═S(═O)H₂, or optionally substituted —NH₂,

the remaining two (without the structure of formula (2) among R¹, R², and R³) are the same or different, each independently a hydrogen atom, halogen, a hydroxyl group, an optionally substituted hydrocarbyl group, or an optionally substituted heterohydrocarbyl group,

R⁴ is

1) —C(═O)R⁸,

2) —SO₂-L⁶-R⁸, (wherein R⁸ in 1) and 2) is a hydroxyl group, an optionally substituted hydrocarbyl group, or an optionally substituted heterohydrocarbyl group, and L⁶ is a single bond or an optionally substituted hydrocarbylene group), 3) —NR^(a4)R^(b3) 4) —B(OR^(m1))₂, 5) —PO(OR^(m1))(OR^(m2)), 6) optionally substituted heteroaryl, 7) an optionally substituted non-aryl heterocycle, or 8) a bioisostere of one of 1) to 7), (wherein the formulas of 1), 2), 4), 5), and 6) include a carboxylic acid isostere, and 8) may include them in duplicates),

R^(a4) and R^(b3) are the same or different, each independently having the same definition as R^(a1), R^(a2), and R^(b1), wherein a combination of R^(a4) and R^(b3), when attached to the same nitrogen atom, together may form an optionally substituted nitrogen-containing non-aryl heterocycle,

R^(m1) is a hydrogen atom or an optionally substituted hydrocarbyl group,

wherein if R^(m1) is attached to a boron atom via an oxygen atom, two R^(m1), as alkylene, together with the boron atom and two oxygen atoms, may form a non-aryl heterocycle (wherein an alkylene moiety is optionally substituted in the non-aryl heterocycle),

R^(m2) is a hydrogen atom or an optionally substituted hydrocarbyl group, and

R⁶¹, R⁶², R⁶³, and R⁶⁴ are each independently a hydrogen atom, halogen, an optionally substituted alkyl group, or -L¹-L²-Z.

[Item 2]

A compound represented by formula (1a) or (1b):

or a pharmaceutically acceptable salt thereof wherein

G is an oxygen atom, a sulfur atom, or —NR^(a1)—,

X is a hydroxyl group, an optionally substituted alkoxy group, or —NR^(a2)R^(b1),

R^(a1), R^(a2), and R^(b1) are the same or different, each independently a hydrogen atom, a hydroxyl group, an optionally substituted hydrocarbyl group, or an optionally substituted heterohydrocarbyl group,

wherein R^(a2) and R^(b1) together may form an optionally substituted nitrogen-containing non-aryl heterocycle,

L¹ is a single bond, an oxygen atom, a sulfur atom, —SO—, —SO₂—, an optionally substituted hydrocarbylene group, or an optionally substituted heterohydrocarbylene group,

L² is a single bond or an optionally substituted hydrocarbylene group,

Z is a hydrogen atom, a hydroxyl group, an optionally substituted hydrocarbyl group, or an optionally substituted heterohydrocarbyl group,

one of R¹, R², and R³ is represented by formula (2):

wherein

Y is an oxygen atom, a sulfur atom, or —NR^(j)—, and R^(j) is a hydrogen atom, a hydroxyl group, or an optionally substituted hydrocarbyl group,

ring A is an optionally substituted non-aryl heterocycle,

L³ is an oxygen atom, a sulfur atom, an optionally substituted hydrocarbylene group, an optionally substituted heterohydrocarbylene group, —S(═O)—, or —S(═O)₂—,

L⁴ is a single bond, an optionally substituted hydrocarbylene group, or —C(═N—OR^(h1))—,

R^(h1) is

1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₁₀ alicyclic group, 4) C₆₋₁₀ aryl, 5) 5- or 6-membered heteroaryl, or 6) a 4- to 10-membered non-aryl heterocycle, (wherein each substituent from 2) to 6) is optionally substituted),

R⁵ is a hydrogen atom, a hydroxyl group, an optionally substituted hydrocarbyl group, or an optionally substituted heterohydrocarbyl group,

the remaining two (without the structure of formula (2) among R¹, R², and R³) are the same or different, each independently a hydrogen atom, halogen, a hydroxyl group, an optionally substituted hydrocarbyl group, or an optionally substituted heterohydrocarbyl group,

R⁴ is

1) —C(═O)R⁸,

2) —SO₂-L⁶-R⁸, (wherein R⁸ in 1) and 2) is a hydroxyl group, an optionally substituted hydrocarbyl group, or an optionally substituted heterohydrocarbyl group, and L⁶ is a single bond or an optionally substituted hydrocarbylene, 3) —NR^(a4)R^(b3), 4) —B(OR^(m1))₂, 5) —PO(OR^(m1))(OR^(m2)), 6) optionally substituted heteroaryl, 7) an optionally substituted non-aryl heterocycle, or 8) a bioisostere of one of 1) to 7), (wherein the formulas of 1), 2), 4), 5), and 6) include a carboxylic acid isostere, and 8) may include them in duplicates),

R^(a4) and R^(b3) are the same or different, each independently having the same definition as R^(a1), R^(a2), and R^(b1), wherein a combination of R^(a4) and R^(b3), when attached to the same nitrogen atom, together may form an optionally substituted nitrogen-containing non-aryl heterocycle,

R^(m1) is a hydrogen atom or an optionally substituted hydrocarbyl group,

wherein if R^(m1) is attached to a boron atom via an oxygen atom, two R^(m1), as alkylene, together with the boron atom and two oxygen atoms, may form a non-aryl heterocycle (wherein an alkylene moiety is optionally substituted in the non-aryl heterocycle),

R^(m2) is a hydrogen atom or an optionally substituted hydrocarbyl group, and

R⁶¹, R⁶², R⁶³, and R⁶⁴ are each independently a hydrogen atom, halogen, an optionally substituted alkyl group, or -L¹-L²-Z.

[Item 3]

The compound or the pharmaceutically acceptable salt thereof according to item 1 or 2, represented by formula (1a) or (1b):

wherein

G is an oxygen atom, a sulfur atom, or —NR^(a1)—,

X is a hydroxyl group, an optionally substituted C₁₋₆ alkoxy group, or —NR^(a2)R^(b1),

R^(a1), R^(a2), and R^(b1) are the same or different, each independently

1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₁₀ alicyclic group, 4) C₆₋₁₀ aryl, 5) 5- or 6-membered heteroaryl, 6) a 4- to 10-membered non-aryl heterocycle, 7) a C₁₋₆ alkylcarbonyl group, 8) a C₃₋₁₀ alicyclic carbonyl group, 9) a C₆₋₁₀ arylcarbonyl group, 10) a 5- or 6-membered heteroarylcarbonyl group, 11) a C₁₋₆ alkylsulfonyl group, 12) a C₃₋₁₀ alicyclic sulfonyl group, 13) a C₆₋₁₀ arylsulfonyl group, 14) a 5- or 6-membered heteroarylsulfonyl group, or

15) —OR^(c1),

(wherein each substituent from 2) to 14) is optionally substituted),

wherein R^(a2) and R^(b1) together may form an optionally substituted 4- to 10-membered nitrogen-containing non-aryl heterocycle,

R^(c1) is

1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₁₀ alicyclic group, 4) C₆₋₁₀ aryl, 5) 5- or 6-membered heteroaryl, or 6) a 4- to 10-membered non-aryl heterocycle, (wherein each substituent from 2) to 6) is optionally substituted),

L¹ is a single bond, an oxygen atom, a sulfur atom, —SO—, —SO₂—, —NR^(d1)—, —NR^(d1)C(═O)—, or —NR^(d1)SO₂—,

L² is a single bond or an optionally substituted C₁₋₆ alkylene group,

Z is

1) a hydrogen atom, 2) a hydroxyl group, 3) a cyano group, 4) a carboxyl group, 5) a C₃₋₁₀ alicyclic group, 6) C₆₋₁₀ aryl, 7) 5- or 6-membered heteroaryl, 8) a 4- to 10-membered non-aryl heterocycle, 9) a C₁₋₆ alkoxy group, 10) a C₃₋₁₀ alicyclic oxy group, 11) a C₆₋₁₀ aryloxy group, 12) a 5- or 6-membered heteroaryloxy group, 13) a 4- to 10-membered non-aryl heterocyclyl oxy group, 14) a C₁₋₆ alkylthio group, 15) a C₃₋₁₀ alicyclic thio group, 16) a C₆₋₁₀ arylthio group, 17) a 5- or 6-membered heteroarylthio group, 18) a 4- to 10-membered non-aryl heterocyclyl thio group, (wherein each substituent from 5) to 18) is optionally substituted), 19) —SO₂—NR^(e1)R^(f1), 20) —NR^(e1)—C(═O)OR^(f1), 21) —NR^(g1)—C(═O)NR^(e1)R^(f1), 22) —NR^(e1)—C(═S)R^(f1), 23) —NR^(e1)—C(═S)OR^(f1), 24) —NR^(g1)—C(═S)NR^(e1)R^(f1), 25) —NR^(g1)—CR^(e1)(═NR^(f1)) 26) —NR^(g1)—CR^(e1)(═N—OR^(e1)), 27) —NR^(h1)—C(═NR^(g1))NR^(e1)R^(f1), 28) —NR^(h1)—C(═N—OR^(g1))NR^(e1)R^(f1), 29) —NR^(i1)—C(═NR^(h1))NR^(g1)—NR^(e1)R^(f1), 30) —NR^(i1)—C(═N—OR^(h1))NR^(g1)—NR^(e1)R^(f1), 31) —NR^(e1)—SO₂—R^(f1), 32) —NR^(g1)—SO₂—NR^(e1)R^(f1),

33) —C(═O)OR^(e1), 34) —C(═S)OR^(e1),

35) —C(═S)NR^(e1)R^(f1), 36) —C(═S)NR^(e1)OR^(f1), 37) —C(═S)NR^(g1)—NR^(e1)R^(f1), 38) —C(═NR^(e1))R^(f1), 39) —C(═N—OR^(e1))R^(f1), 40) —C(═NR^(h1))NR^(g1)—NR^(e1)R^(f1), 41) —C(═N—OR^(h1))NR^(g1)—NR^(e1)R^(f1), 42) —NR^(e1)R^(f1), 43) —NR^(g1)—NR^(e1)R^(f1), 44) —NR^(e1)OR^(f1), 45) —NR^(e1)—C(═O)R^(f1), 46) —C(═O)NR^(e1)R^(f1), 47) —C(═O)NR^(e1)OR^(f1), 48) —C(═O)NR^(g1)—NR^(e1)R^(f1),

49) —C(═O)R^(e1),

50) —C(═NR^(g1))NR^(e1)R^(f1), or 51) —C(═N—OR^(h1))NR^(e1)R^(f1),

one of R¹, R², and R³ is a group represented by formula (2):

wherein

Y is an oxygen atom, a sulfur atom, or —NR^(j)—,

ring A is an optionally substituted 4- to 20-membered non-aryl heterocycle,

L³ is

1) an oxygen atom, 2) a sulfur atom,

3) —NR^(d2)—, 4) —NR^(d2)C(═O)—,

5) —NR^(d2)SO₂—, 6) a C₁₋₆ alkylene group, 7) a C₃₋₁₀ cycloalkylene group, 8) a 4- to 10-membered non-aryl heterocyclylene group, (wherein each substituent from 6) to 8) is optionally substituted),

9) —C(═O)—, 10) —S(═O)—, or 11) —S(═O)₂—,

L⁴ is

1) a single bond, 2) a C₁₋₆ alkylene group, 3) a C₃₋₁₀ cycloalkylene group, 4) a C₆₋₁₀ arylene group, 5) a 5- or 6-membered heteroarylene group, 6) a 4- to 10-membered non-aryl heterocyclylene group, (wherein each substituent from 2) to 6) is optionally substituted), or

7) —C(═N—OR^(h1))—,

R⁵ is

1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₁₀ alicyclic group, 4) a 4- to 10-membered non-aryl heterocycle, 5) C₆₋₁₀ aryl, 6) 5- to 10-membered heteroaryl, 7) a C₁₋₆ alkylthio group, (wherein each substituent from 2) to 7) is optionally substituted, and if two substituents further substituted with the substituent of 1), 2), or 3) are each substituted on adjacent atoms within a ring, the two substituents together may further form a condensed ring structure),

8) —NR^(e1)OH,

9) a carboxyl group (—C(═O)OH) 10) a carboxylic acid isostere (wherein the carboxylic acid isostere comprises an ester group-C(═O)OR^(20a), 11) a sulfo group (sulfonic acid group), 12) —SO₂R^(e1), 13) —SO₂—NR^(e1)R^(f1), 14) —S(═O)(═NR^(f1))R^(e1), 15) —NR^(e1)—C(═O)R^(f1), 16) —NR^(e1)—C(═O)OR^(f1), 17) —NR^(g1)—C(═O)NR^(e1)R^(f1), 18) —NR^(e1)—SO₂—R^(f1), 19) —NR^(g1)—SO₂—NR^(e1)R^(f1), 20) —N═S(═O)R^(e1)R^(f1), 21) —C(═O)NR⁵⁰R⁵¹, or 22) —NR^(e1)R^(f1) (wherein if R⁵ is the substituent of 22), -L³-L⁴-R⁵ is not —(CH₂)₁₋₄NR^(e1)R^(f1) (wherein R^(e1) and R^(f1) are a hydrogen atom, optionally substituted C₁₋₄ alkyl, an optionally substituted C₃₋₇ alicyclic group, an optionally substituted 4- to 10-membered non-aryl heterocyclic group, optionally substituted C₆₋₁₀ aryl, or optionally substituted 5- to 10-membered heteroaryl)),

R^(20a) is

1) a C₁₋₆ alkyl group, 2) a C₃₋₁₀ alicyclic group, 3) C₆₋₁₀ aryl, 4) 5- or 6-membered heteroaryl, or 5) a 4- to 10-membered non-aryl heterocycle, (wherein each substituent from 1) to 5) is optionally substituted),

-   -   R⁵⁰ represents         1) a hydrogen atom,         2) a C₁₋₆ alkyl group,         3) a hydroxyl group,         4) a C₁₋₆ alkoxy group,         5) a C₃₋₆ cycloalkoxy group,         6) a C₃₋₆ alicyclic group,         7) a 4- to 6-membered non-aryl heterocycle,         8) C₆₋₁₀ aryl,         9) 5- to 10-membered heteroaryl 10) 4- to 6-membered non-aryl         heterocyclyl oxy,         11) C₆₋₁₀ aryloxy,         12) 5- to 10-membered heteroaryloxy,         13) a C₁₋₆ alkylsulfonyl group,         14) a C₃₋₆ cycloalkoxysulfonyl group, or         15) a 4- to 6-membered non-aryl heterocyclyl sulfonyl group,         (wherein each substituent of 2) and 4) to 15) is optionally         substituted),

R⁵¹ represents

1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₆ alicyclic group, 4) a 4- to 6-membered non-aryl heterocycle, 5) C₆₋₁₀ aryl, or 6) 5- to 10-membered heteroaryl, (wherein each substituent from 2) to 6) is optionally substituted), or

R⁵⁰ and R⁵¹ together may form optionally substituted 4- to 7-membered nitrogen-containing non-aryl heterocycle,

the remaining two (without the structure of formula (2) among R¹, R², and R³) are the same or different, each independently a hydrogen atom, a halogen atom, an optionally substituted C₁₋₆ alkyl group, an optionally substituted C₁₋₆ alkoxy group, an optionally substituted C₁₋₆ alkylthio group, optionally substituted 5- or 6-membered heteroaryl, or —NR^(a3)R^(b2),

R^(d1), R^(d2), R^(e1), R^(f1), R^(g1), R^(h1), R^(i1), and R^(j) are the same or different, each independently

1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₁₀ alicyclic group, 4) C₆₋₁₀ aryl, 5) 5- or 6-membered heteroaryl, or 6) a 4- to 10-membered non-aryl heterocycle, (wherein each substituent from 2) to 6) is optionally substituted),

a combination of R^(e1) and R^(f1), when attached to the same nitrogen atom, together may form an optionally substituted 4- to 10-membered nitrogen-containing non-aryl heterocycle,

R⁴ is

1) —C(═O)R⁸,

2) —SO₂-L⁶-R⁸, (wherein R⁸ in 1) and 2) is —NR^(a5)R^(b4), —NR^(a5)-L⁷-B(OR^(m1))₂, —OR^(m1), or an optionally substituted C₁₋₆ alkyl group, and L⁶ is a single bond or —NR^(a6)—), 3) —NR^(a4)R^(b3), 4) —B(OR^(m1))₂, 5) —PO(OR^(m1))(OR^(m2)), 6) optionally substituted 5-membered heteroaryl, 7) an optionally substituted 5-membered non-aryl heterocycle, or 8) a bioisostere of one of 1) to 7), (wherein the formulas of 2), 4), 5), and 6) include a carboxylic acid isostere, and 8) may include them in duplicates),

R^(a3), R^(a4), R^(a5), R^(a6), R^(b2), R^(b3), and R^(b4) are the same or different, each independently having the same definition as R^(a1), R^(a2), and R^(b1), wherein a combination of R^(a3) and R^(b2), R^(a4) and R^(b3), or R^(a5) and R^(b4), when attached to the same nitrogen atom, together may form an optionally substituted 4- to 10-membered nitrogen-containing non-aryl heterocycle,

R^(m1) is

1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₁₀ alicyclic group, 4) C₆₋₁₀ aryl, 5) 5- or 6-membered heteroaryl, or 6) a 4- to 10-membered non-aryl heterocycle, (wherein each substituent from 2) to 6) is optionally substituted),

wherein if R^(m1) is attached to a boron atom via an oxygen atom, two R^(m1), as C₂₋₄ alkylene, together with the boron atom and two oxygen atoms, may form a 5- to 7-membered non-aryl heterocycle (wherein an alkylene moiety is optionally substituted in the non-aryl heterocycle),

R^(m2) is a hydrogen atom, an optionally substituted C₁₋₆ alkyl group, or an optionally substituted C₃₋₁₀ alicyclic group,

L⁷ is an optionally substituted C₁₋₃ alkylene group,

R⁶¹, R⁶², and R⁶³ are each independently a hydrogen atom, halogen, or an optionally substituted C₁₋₆ alkyl group, and

R⁶⁴ is a hydrogen atom, halogen, an optionally substituted C₁₋₆ alkyl group, or -L¹-L²-Z.

[Item 4]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 3, wherein L³ is

1) a C₁₋₆ alkylene group, 2) a C₃₋₁₀ cycloalkylene group, or 3) a 4- to 10-membered non-aryl heterocyclylene group, (wherein each substituent from 1) to 3) is optionally substituted), and

L⁴ is a single bond or an optionally substituted C₁₋₅ alkylene group.

[Item 5]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 4, wherein

L³ is an optionally substituted C₁₋₄ alkylene group, and

L⁴ is a single bond or an optionally substituted C₁₋₃ alkylene group.

[Item 6]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 5, wherein

L³ is —(CR³⁰R³¹)_(n1)—,

R³⁰ and R³¹ are each independently, or if there are multiple instances of each of them, all of them independently represent

1) a hydrogen atom, 2) —NR^(a7)R^(a8), 3) a C₁₋₄ alkyl group, 4) C₆₋₁₀ aryl, 5) 5- to 10-membered heteroaryl, 6) a C₃₋₆ alicyclic group, 7) a 4- to 10-membered non-aryl heterocycle, (wherein each substituent from 3) to 7) is optionally substituted), or

8) —OR^(c2), or

R³⁰ and R³¹, together with the carbon atom to which they are attached, form a C₃₋₆ alicyclic group or a 4- to 6-membered non-aryl heterocycle,

R^(a7) and R^(a8) are the same or different, each independently

1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₁₀ alicyclic group, 4) C₆₋₁₀ aryl, 5) 5- or 6-membered heteroaryl, 6) a 4- to 10-membered non-aryl heterocycle, 7) a C₁₋₆ alkylcarbonyl group, 8) a C₃₋₁₀ alicyclic carbonyl group, 9) a C₆₋₁₀ arylcarbonyl group, 10) a 5- or 6-membered heteroarylcarbonyl group, 11) a C₁₋₆ alkylsulfonyl group, 12) a C₃₋₁₀ alicyclic sulfonyl group, 13) a C₆₋₁₀ arylsulfonyl group, 14) a 5- or 6-membered heteroarylsulfonyl group, or

15) —OR^(c3),

(wherein each substituent from 2) to 14) is optionally substituted),

wherein R^(a7) and R^(a8) together may form an optionally substituted 4- to 10-membered nitrogen-containing non-aryl heterocycle,

R^(c2) and R^(c3) are each independently

1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₁₀ alicyclic group, 4) C₆₋₁₀ aryl, 5) 5- or 6-membered heteroaryl, or 6) a 4- to 10-membered non-aryl heterocycle, (wherein each substituent from 2) to 6) is optionally substituted),

n1 is an integer 1, 2, 3, or 4,

L⁴ is —(CR⁴⁰R⁴¹)_(n2)—,

R⁴⁰ and R⁴¹ each independently, or if there are multiple instances of each of them, all of them independently represent

1) a hydrogen atom, 2) —NR^(a9)R^(a10), 3) a C₁₋₄ alkyl group, 4) C₆₋₁₀ aryl, 5) 5- to 10-membered heteroaryl, 6) a C₃₋₆ alicyclic group 7) a 4- to 10-membered non-aryl heterocycle, (wherein each substituent from 3) to 7) is optionally substituted), or

8) —OR^(c4), or

R⁴⁰ and R⁴¹, together with the carbon atom to which they are attached, form a C₃₋₆ alicyclic group or a 4- to 6-membered non-aryl heterocycle,

R^(a9) and R^(a10) are the same or different, each independently

1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₁₀ alicyclic group, 4) C₆₋₁₀ aryl, 5) 5- or 6-membered heteroaryl, 6) a 4- to 10-membered non-aryl heterocycle, 7) a C₁₋₆ alkylcarbonyl group, 8) a C₃₋₁₀ alicyclic carbonyl group, 9) a C₆₋₁₀ arylcarbonyl group, 10) a 5- or 6-membered heteroarylcarbonyl group, 11) a C₁₋₆ alkylsulfonyl group, 12) a C₃₋₁₀ alicyclic sulfonyl group, 13) a C₆₋₁₀ arylsulfonyl group, 14) a 5- or 6-membered heteroarylsulfonyl group, (wherein each substituent from 2) to 14) is optionally substituted), or

15) —OR^(c5),

wherein R^(a9) and R^(a10) together may form an optionally substituted 4- to 10-membered nitrogen-containing non-aryl heterocycle,

R^(c4) and R^(c5) are each independently defined the same as R^(c2) and R^(c3), and

n2 is an integer 0 (i.e., when L⁴ is a single bond), 1, 2, or 3.

[Item 7]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 6, wherein

-L³-L⁴- is an optionally substituted C₁₋₂ alkylene group.

[Item 8]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 7, wherein -L³-L⁴- is a C₁₋₂ alkylene group optionally substituted with a C₁₋₃ alkyl group, an amino group, or a hydroxymethyl group, or a plurality of the same or different groups thereamong (wherein two C₁₋₃ alkyl groups, when attached to the same carbon atom, together with the carbon atom to which they are attached, may form a C₃₋₆ alicyclic group).

[Item 9]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 8, wherein

R⁵ is

1) a C₃₋₁₀ alicyclic group, 2) C₆₋₁₀ aryl, 3) 5- to 10-membered heteroaryl, 4) a C₁₋₆ alkylthio group, (wherein each substituent from 1) to 4) is optionally substituted, and if two substituents further substituted with the substituent of 2) or 3) are each substituted on adjacent atoms within a ring, the two substituents together may further form a condensed ring structure),

5) —NR^(e1)OH,

6) —C(═O)NR⁵⁰R⁵¹, 7) —SO₂—NR^(e1)R^(f1), 8) —NR^(e1)—SO₂—R^(f1),

9) —C(═O)OR²⁰, or

10) —NR^(e1)R^(f1) (wherein if R⁵ is the substituent of 10), L³ and/or L⁴ is a C₁₋₆ alkylene group that is necessarily substituted with one or more groups other than a hydrogen atom (wherein L³ or L⁴, together with said substituent, may form a C₃₋₁₀ alicyclic group or a 4- to 10-membered non-aryl heterocycle)), and

R²⁰ is

1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₁₀ alicyclic group, 4) C₆₋₁₀ aryl, 5) 5- or 6-membered heteroaryl, or 6) a 4- to 10-membered non-aryl heterocycle, (wherein each substituent from 2) to 6) is optionally substituted).

[Item 10]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 9, wherein

R⁵ is

1) C₆₋₁₀ aryl, 2) 5- to 10-membered heteroaryl, 3) —C(═O)NR⁵⁰R⁵¹,

4) —C(═O)OR²⁰, or

5) —NR^(e1)R^(f1) (wherein if R⁵ is the substituent of 5), L³ and/or L⁴ is a C₁₋₆ alkylene group that is necessarily substituted with one or more groups other than a hydrogen atom, and together with said substituent forms at least one C₃₋₁₀ alicyclic group or 4- to 10-membered non-aryl heterocycle) (wherein each substituent from 1) to 2) is optionally substituted, and any two groups thereof, when each is attached to adjacent atoms within a ring, together may further form a condensed ring structure).

[Item 11]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 10, wherein Z-L²-L¹ is an optionally substituted C₁₋₆ alkylthio group.

[Item 12]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 11, wherein R⁶¹, R⁶², R⁶³, and R⁶⁴ are each independently a hydrogen atom, a fluorine atom, or a C₁₋₃ alkyl group optionally substituted with a fluorine atom.

[Item 13]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 12, wherein R⁶¹, R⁶², R⁶³, and R⁶⁴ are each independently a hydrogen atom or a fluorine atom.

[Item 14]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 13, wherein G is an oxygen atom.

[Item 15]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 14, wherein X is a hydroxyl group or an optionally substituted C₁₋₆ alkoxy group.

[Item 16]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 15, wherein X is a hydroxyl group.

[Item 17]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 16, wherein the compounds of formulas (1a) and (1b) are represented by formulas (3a) and (3b), respectively:

wherein X, R¹, R², and R³ are defined the same as any one of items 1 to 16, and

R⁴ is selected from the group consisting of

1) —C(═O)OR^(m1) (wherein R^(m1) is a hydrogen atom, a C₁₋₆ alkyl group, a C₃₋₁₀ alicyclic group, C₆₋₁₀ aryl, 5- or 6-membered heteroaryl, or a 4- to 10-membered non-aryl heterocycle, wherein the C₁₋₆ alkyl group, the C₃₋₁₀ alicyclic group, the C₆₋₁₀ aryl, the 5- or 6-membered heteroaryl, and the 4- to 10-membered non-aryl heterocycle are each optionally substituted), and 2) a bioisostere of 1).

[Item 18]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 17, wherein R⁴ is

1) —C(═O)OH (i.e., a carboxyl group), or 2) a carboxylic acid isostere.

[Item 19]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 18, wherein the compounds of formulas (1a) and (1b) or the compounds of formulas (3a) and (3b) are represented by formulas (4a) and (4b), respectively:

wherein X, R⁴, Y, ring A, L³, L⁴, and R⁵ are defined the same as any one of items 1 to 18, and

R¹ and R² are the same or different, each independently a hydrogen atom, a halogen atom, a C₁₋₆ alkyl group, a C₁₋₆ alkoxy group, or a C₁₋₆ alkylthio group (wherein the C₁₋₆ alkyl group, C₁₋₆ alkoxy group, and C₁₋₆ alkylthio group are optionally substituted).

[Item 20]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 19, wherein ring A is an optionally substituted 4- to 10-membered non-aryl heterocycle.

[Item 21]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 20, wherein ring A is an optionally substituted 4- to 7-membered non-aryl heterocycle.

[Item 22]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 21, wherein Y is an oxygen atom or a sulfur atom.

[Item 23]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 22, wherein Y is an oxygen atom.

[Item 24]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 23, wherein the compounds of formulas (1a) and (1b), the compounds of formulas (3a) and (3b), or the compounds of formulas (4a) and (4b) are represented by formulas (5a) and (5b), respectively:

wherein R¹, R², Y, L³, L⁴, and R⁵ are defined the same as any one of items 1 to 23, and ring A is an optionally substituted 4- to 6-membered nitrogen-containing non-aryl heterocycle.

[Item 25]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 3 and 11 to 24, wherein L³ is —C(═O)— or —S(═O)₂—.

[Item 26]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 3 and 11 to 25, wherein L³ is —C(═O)—.

[Item 27]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 3 and 11 to 26, wherein L⁴ is a single bond, —C(═N—OR^(h1))—, or an optionally substituted C₁₋₆ alkylene group, wherein R^(h1) is an optionally substituted C₁₋₆ alkyl group.

[Item 28]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 27, wherein R¹ and R² are the same or different, each independently selected from the group consisting of

1) a hydrogen atom, 2) a halogen atom, 3) a C₁₋₆ alkyl group, 4) a C₁₋₆ alkoxy group, and 5) a C₁₋₆ alkylthio group, (wherein each substituent from 3) to 5) is optionally substituted).

[Item 29]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 28, wherein R¹ and R² are the same or different, each independently selected from the group consisting of

1) a hydrogen atom, 2) a halogen atom, 3) a C₁₋₆ alkyl group, 4) a C₁₋₆ alkoxy group, and 5) a C₁₋₆ alkylthio group, (wherein each substituent from 3) to 5) is optionally substituted with a halogen atom).

[Item 30]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 29, wherein R¹ and R² are the same or different, each independently selected from the group consisting of

1) a hydrogen atom, 2) a halogen atom, and 3) a C₁₋₆ alkyl group optionally substituted with a halogen atom.

[Item 31]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 30, wherein R¹ and R² are the same or different, each independently selected from the group consisting of

1) a hydrogen atom, 2) a fluorine atom, and 3) a C₁₋₃ alkyl group optionally substituted with a fluorine atom.

[Item 32]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 31, wherein R¹ and R² are both hydrogen atoms.

[Item 33]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 32, wherein the compounds of formulas (1a) and (1b), the compounds of formulas (3a) and (3b), the compounds of formulas (4a) and (4b), or the compounds of formulas (5a) and (5b) are represented by formulas (6a) and (6b), respectively:

wherein

L³, L⁴, and R⁵ are defined the same as any one of items 1 to 32,

m is an integer 1, 2, or 3,

n is an integer 1, 2, or 3, and

m+n is 2, 3, or 4.

[Item 34]

The compound or the pharmaceutically acceptable salt thereof according to item 33, wherein the compounds of formulas (6a) and (6b) are enantiomers represented by formulas (7a) and (7b):

formulas (8a) and (8b):

respectively wherein

L³, L⁴, and R⁵ are defined the same as any one of items 1 to 33, and

m and n are defined the same as item 33.

[Item 35]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 34, wherein m is 1 or 2, n is 1 or 2, and m+n is 2 or 3.

[Item 36]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 35, wherein m is 1, and n is 1.

[Item 37]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 6, 9 to 24, and 28 to 36, wherein

L³ is —(CR³⁰R³¹)_(n1)— or 4- to 10-membered non-aryl heterocyclylene,

R³⁰ and R³¹ each independently, or if there are multiple instances of each of them, all of them independently represent

1) a hydrogen atom, 2) an optionally substituted C₁₋₄ alkyl group, or 3) optionally substituted C₆₋₁₀ aryl,

n1 is 1, 2, or 3,

L⁴ is a single bond or —(CR⁴⁰R⁴¹)_(n2)—,

R⁴⁰ and R⁴¹ each independently, or if there are multiple instances of each of them, all of them independently represent

1) a hydrogen atom, 2) —NR^(a9)R^(a10), 3) an optionally substituted C₁₋₄ alkyl group, or

4) —OR^(c4) or

R⁴⁰ and R⁴¹, together with the carbon atom to which they are attached, form a C₃₋₆ alicyclic group or a 4- to 6-membered non-aryl heterocycle,

R^(a9), R^(a10), and R^(c4) are the same or different, each independently

1) a hydrogen atom, 2) an optionally substituted C₁₋₆ alkyl group, or 3) an optionally substituted C₃₋₁₀ alicyclic group, wherein R^(a9) and R^(a10) together may form an optionally substituted 4- to 10-membered nitrogen-containing non-aryl heterocycle, and

n2 is 0, 1, or 2.

[Item 38]

The compound or the pharmaceutically acceptable salt thereof according to item 37, wherein n1 is 1 or 2, and n2 is 0 or 1.

[Item 39]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 6, 9 to 24, and 28 to 38, wherein

L³ is —CR³⁰R³¹— or 4- to 10-membered non-aryl heterocyclylene,

R³⁰ and R³¹ each independently represent,

1) a hydrogen atom, 2) a C₁₋₄ alkyl group (wherein the group is optionally substituted with halogen, —NR^(a11)R^(a12), or —OR^(c6)), or 3) C₆ aryl (wherein the group is optionally substituted with halogen, —NR^(a13)R^(a14), —OR^(c7), or a C₁₋₃ alkyl group (wherein the group is optionally substituted with halogen, —NR^(a15)R^(a16), or —OR^(c8))),

L⁴ is a single bond or —(CR⁴⁰R⁴¹)_(n2)—,

R⁴⁰ and R⁴¹ each independently represent,

1) a hydrogen atom, 2) —NR^(a9)R^(a10), 3) a C₁₋₄ alkyl group (wherein the group is optionally substituted with halogen, —NR^(a17)R^(a18), or —OR^(c9)), or

4) —OR^(c4), or

R⁴⁰ and R⁴¹, together with the carbon atom to which they are attached, form a C₃₋₆ alicyclic group,

R^(a9), R^(a10), R^(a11), R^(a12), R^(a13), R^(a14), R^(a15), R^(a16), R^(a17), R^(a18), R^(c4), R^(c6), R^(c7), R^(c8), and R^(c9) are the same or different, each independently representing

1) a hydrogen atom, or 2) a C₁₋₄ alkyl group (wherein the group is optionally substituted with halogen, —NR^(a19)R^(a20), or —OR^(c10)),

R^(a19), R^(a20), and R^(c10) are the same or different, each independently representing

1) a hydrogen atom, or 2) a C₁₋₄ alkyl group (wherein the group is optionally substituted with halogen),

wherein each combination of R^(a9) and R^(a10), R^(a11) and R^(a12), R^(a13) and R^(a14), R^(a15) and R^(a16), R^(a17) and R^(a18), or R^(a19) and R^(a20) together may form an optionally substituted 4- to 7-membered nitrogen-containing non-aryl heterocycle, and

n2 is 0 or 1.

[Item 40]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 6, 9 to 24, and 28 to 39, wherein

L³ is —CH₂—, —CH(CH₂NH₂)—, or —CH(CH₂OH)—, and

L⁴ is a single bond, —CH₂—, —CH(NH₂)—, —CMe(NH₂)—, —CEt(NH₂)—, —C(iso-Pr)(NH₂)—, —CH(CH₂NH₂)—, —CH(OH)—, —CH(CH₂OH)—, —C(CH₂OH)₂—, or

[Item 41]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 6, 9 to 24, and 28 to 39, wherein L³ is 4- to 10-membered non-aryl heterocyclylene.

[Item 42]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 6, 9 to 24, 28 to 39, and 41, wherein L³ is 5-membered non-aryl heterocyclylene.

[Item 43]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 6, 9 to 24, 28 to 39, and 41 to 42, wherein L³ is

[Item 44]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 6, 9 to 24, 28 to 39, and 41 to 43, wherein L⁴ is a single bond.

[Item 45]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 24 and 28 to 40, wherein R⁵ is 1) C₆₋₁₀ aryl, or

2) 5- to 10-membered heteroaryl, (wherein each substituent from 1) to 2) is optionally substituted, and if two substituents further substituted with the substituent of 1) or 2) are each substituted on adjacent atoms within a ring, the two substituents together may further form a condensed ring structure).

[Item 46]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 24 and 28 to 45, wherein

R⁵ is C₆ aryl (i.e., phenyl) or 5-membered, 6-membered, 9-membered, or 10-membered heteroaryl,

each group of R⁵ is optionally substituted with each of Ra or R^(6b) at all chemically substitutable positions on a carbon atom or a nitrogen atom within a ring thereof,

wherein R^(6a), which are substituents on the carbon atom, if there are multiple instances on the same ring, are all independently selected from the group consisting of

1) a hydrogen atom, 2) a hydroxyl group, 3) a cyano group, 4) halogen, 5) a C₁₋₄ alkyl group, 6) a C₃₋₁₀ alicyclic group, 7) a C₁₋₄ alkoxy group, 8) a C₃₋₁₀ alicyclic oxy group, 9) a C₆₋₁₀ aryloxy group, 10) a 5- or 6-membered heteroaryloxy group, 11) a 4- to 10-membered non-aryl heterocyclyl oxy group, (wherein each substituent from 5) and 11) is optionally substituted), 12) —SO₂—NR^(e2)R^(f2), 13) —NR^(g2)—CR^(e2)(═NR^(f2)), 14) —NR^(g2)—CR^(e2)(═N—OR^(f2)), 15) —NR^(h2)—C(═NR^(g2))NR^(e2)R^(f2), 16) —NR^(h2)—C(═N—OR^(g2))NR^(e2)R^(f2), 17) —NR^(i2)—C(═NR^(h2))NR^(g2)—NR^(e2)R^(f2), 18) —NR^(i2)—C(═N—OR^(h2))NR^(g2)—NR^(e2)R^(f2), 19) —C(═NR^(e2))R^(f2), 20) —C(═N—OR^(e2))R^(f2), 21) —C(═NR^(h2))—NR^(e2)R^(f2), 22) —C(═NR^(h2))NR^(g2)—NR^(e2)R^(f2), 23) —C(═N—OR^(h2))NR^(g2)—NR^(e2)R^(f2), 24) —NR^(e2)R^(f2), 25) —NR^(g2)—NR^(e2)R^(f2), 26) —NR^(e2)OR^(f2), 27) —NR^(e2)—C(═O)R^(f2), 28) —C(═O)NR^(e2)R^(f2), 29) —C(═O)NR^(e2)OR^(f2), 30) —C(═O)NR^(g2)—NR^(e2)R^(f2),

31) —C(═O)R^(e2), 32) —C(═O)OR^(e2), and

33) —C(═N—OR^(h2))NR^(e2)R^(f2),

R^(6b), which are substituents on the nitrogen atom, if there are multiple instances on the same ring, are all independently selected from the group consisting of

1) a hydrogen atom, 2) a hydroxyl group, 3) a C₁₋₄ alkyl group (wherein the alkyl group is optionally substituted), 4) a C₃₋₁₀ alicyclic group (wherein the alicyclic group is optionally substituted), 5) —C(═NR^(e2))R^(f2), 6) —C(═N—OR^(e2))R^(f2), 7) —SO₂—NR^(e2)R^(f2), 8) —C(═NR^(h2))—NR^(e2)R^(f2), 9) —C(═NR^(h2))NR^(g2)—NR^(e2)R^(f2), 10) —C(═N—OR^(h2))NR^(g2)—NR^(e2)R^(f2), 11) —C(═O)NR^(e2)R^(f2), 12) —C(═O)NR^(e2)OR^(f2), 13) —C(═O)NR^(g2)—NR^(e2)R^(f2),

14) —C(═O)R^(e2), and

15) —C(═N—OR^(h2))NR^(e2)R^(f2), or

if a combination of two R^(6a) or R^(6a) and R^(6b) are each substituted on adjacent atoms within a ring, the two substituents together may form an optionally substituted 5- to 6-membered heteroaryl ring or an optionally substituted 5- to 7-membered non-aryl heterocycle, which further fuses to an attachment moiety between the adjacent atoms within the ring,

R^(e2), R^(f2), R^(g2), R^(h2), and R^(i2) are the same or different, each independently

1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₁₀ alicyclic group, 4) C₆₋₁₀ aryl, 5) 5- or 6-membered heteroaryl, or 6) a 4- to 10-membered non-aryl heterocycle, (wherein each substituent from 2) to 6) is optionally substituted), and a combination of R^(e2) and R^(f2), when attached to the same nitrogen atom, together may form an optionally substituted 4- to 10-membered nitrogen-containing non-aryl heterocycle.

[Item 47]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 24 and 28 to 46, wherein

R⁵ is C₆ aryl or 5-membered, 6-membered, 9-membered, or 10-membered heteroaryl selected from the group consisting of

d is the number of chemically substitutable positions on a ring of each group by R^(6a), and

each R^(6a) and each R^(6b) are defined the same as item 46.

[Item 48]

The compound or the pharmaceutically acceptable salt thereof according to item 46 or 47, wherein

R⁶, if there are multiple instances on the same ring, are all independently selected from the group consisting of

1) a hydrogen atom, 2) a hydroxyl group, 3) halogen, 4) a C₁₋₄ alkyl group (wherein the alkyl group is optionally substituted with NR^(e2)R^(f2), —C(═O)OR^(f2), —C(═O)NR^(e2)R^(f2), —C(═O)NR^(e2)(OR^(f2)), or a hydroxyl group), 5) a C₁₋₄ alkoxy group 6) —NR^(e2)R^(f2), 7) —C(═O)NR^(e2)R^(f2), and

8) —C(═O)OR^(e2), and

each of R^(6b), if there are multiple instances on the same ring, are all independently selected from the group consisting of

1) a hydrogen atom, 2) a hydroxyl group, and 3) a C₁₋₄ alkyl group (wherein the alkyl group is optionally substituted with NR^(e2)R^(f2), —C(═O)OR^(f2), —C(═O)NR^(e2)R^(f2), —C(═O)NR^(e2)(OR^(f2)), or a hydroxyl group).

[Item 49]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 24 and 28 to 48, wherein R^(e2) and R^(f2) are the same or different, each independently a hydrogen atom, an optionally substituted C₁₋₆ alkyl group, or an optionally substituted C₃₋₁₀ alicyclic group.

[Item 50]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 24 and 28 to 49, wherein R^(e2) and R^(f2) are the same or different, each independently a hydrogen atom or an optionally substituted C₁₋₆ alkyl group.

[Item 51]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 24 and 28 to 50, wherein R^(e2) and R^(f2) are hydrogen atoms.

[Item 52]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 46 to 51, wherein R⁶ is —NR^(e2)R^(f2), and one of R^(e2) and R^(f2) is a hydrogen atom and the other is a C₁₋₄ alkyl group (wherein the alkyl group is optionally substituted with an amino group or a hydroxyl group).

[Item 53]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 24 and 28 to 44, wherein R⁵ is —C(═O)NR⁵⁰R⁵¹.

[Item 54]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 24, 28 to 40, and 53, wherein

R⁵⁰ represents

1) a hydrogen atom, 2) an optionally substituted C₁₋₄ alkyl group, 3) a hydroxyl group, 4) an optionally substituted C₁₋₄ alkoxy group, or 5) an optionally substituted C₁₋₆ alkylsulfonyl group,

R⁵¹ represents

1) a hydrogen atom, or 2) an optionally substituted C₁₋₄ alkyl group, or

R⁵⁰ and R⁵¹ together may form a 4- to 6-membered nitrogen-containing non-aryl heterocycle.

[Item 55]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 24, 28 to 40, and 53 to 54, wherein

R⁵⁰ represents

1) a hydrogen atom, 2) a C₁₋₄ alkyl group (wherein the group is optionally substituted with halogen, a C₃₋₆ alicyclic group, —NR^(a21)R^(a22), or —OR^(c11)), 3) a hydroxyl group, 4) a C₁₋₄ alkoxy group (wherein the group is optionally substituted with halogen, a C₃₋₆ alicyclic group, —NR^(a23)R^(a24), or —OR^(c12), or 5) a C₁₋₄ alkylsulfonyl group (wherein the group is optionally substituted with halogen, a C₃₋₆ alicyclic group, —NR^(a21)R^(a22), or —OR^(c11)),

R^(a21), R^(a22), R^(a23), R^(a24), R^(c11), and R^(c12) are the same or different, each independently representing

1) a hydrogen atom, or 2) a C₁₋₄ alkyl group (wherein the group is optionally substituted with halogen),

wherein each combination of R^(a21) and R^(a22) or R^(a23) and R^(a24) together may form an optionally substituted 4- to 7-membered nitrogen-containing non-aryl heterocycle, and

R⁵¹ is a hydrogen atom or C₁₋₄ alkyl (wherein the group is optionally substituted with halogen).

[Item 56]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 24, 28 to 40, and 53 to 55, wherein

R⁵⁰ represents

1) a hydrogen atom, 2) a C₁₋₄ alkyl group (wherein the group is optionally substituted with a cyclopropyl group, —NH₂, —NHMe, —C(═O)NH₂, —C(═O)NHMe, —C(═O)NMe₂, or a -hydroxyl group), 3) a hydroxyl group, 4) a C₁₋₄ alkoxy group (wherein the group is optionally substituted with a cyclopropyl group, —NH₂, —NHMe, or a -hydroxyl group), or 5) a C₁₋₄ alkylsulfonyl group, and

R⁵¹ is a hydrogen atom.

[Item 57]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 24 and 28 to 40, wherein R⁵ is —C(═O)OR²⁰.

[Item 58]

The compound or the pharmaceutically acceptable salt thereof according to item 57, wherein R² is

1) a hydrogen atom, or 2) an optionally substituted C₁₋₄ alkyl group.

[Item 59]

The compound or the pharmaceutically acceptable salt thereof according to item 56 or 58, wherein

L³ is —CH₂—, and

L⁴ is a single bond, —CH(NH₂)—, or —CMe(NH₂)—.

[Item 60]

The compound or the pharmaceutically acceptable salt thereof according to item 59, wherein L⁴ is

[Item 61]

The compound or the pharmaceutically acceptable salt thereof according to item 59 or 60, wherein L⁴ is

[Item 62]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 57 to 61, wherein R²⁰ is a hydrogen atom.

[Item 63]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 24 and 28 to 40, wherein

R⁵ is —NR^(e1)R^(f1),

L³ is —CH₂—,

L⁴ is —CR⁴⁰R⁴¹—, and

R⁴⁰ and R⁴¹ are each independently a C₁₋₄ alkyl group substituted with a hydroxyl group, or together with the carbon atom to which they are attached, form a C₃₋₆ alicyclic group.

[Item 64]

The compound or the pharmaceutically acceptable salt thereof according to item 63, wherein

R^(e1) and R^(f1) are the same or different, each independently

1) a hydrogen atom, or 2) an optionally substituted C₁₋₃ alkyl group, and

L⁴ is

[Item 65]

The compound or the pharmaceutically acceptable salt thereof according to item 63, wherein

R^(e1) and R^(f1) are the same or different, each independently

1) a hydrogen atom, or 2) an optionally substituted C₁₋₃ alkyl group, and

L⁴ is a C₁₋₄ alkylene group substituted with a hydroxyl group.

[Item 66]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 3 and 11 to 36, wherein L⁴ is a single bond, or a C₁₋₆ alkylene group optionally substituted with —NR²¹R²² or ═NOR²³, wherein R², R², and R² are each independently a hydrogen atom, an optionally substituted C₁₋₆ alkyl group, or an optionally substituted 4- to 10-membered non-aryl heterocyclyl carbonyl group.

[Item 67]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 3, 11 to 36, and 66, wherein L⁴ is a single bond, —CH₂—, —CH(NH₂)—, —CMe(NH₂)—, —CH(NHMe)-, —CD(NH₂)— (wherein D represents a heavy hydrogen atom), —CH₂CH₂—, or —CH(NH₂)—CH₂—, wherein if an amino group is present in L⁴, carbon that attaches to the amino group attaches to L³.

[Item 68]

The compound or the pharmaceutically acceptable salt thereof according to item 67, wherein

L³ is —C(═O)—, and

L⁴ is a single bond, —CH₂—, —CH(NH₂)—, —CMe(NH₂)—, or —CH(NH₂)—CH₂—.

[Item 69]

The compound or the pharmaceutically acceptable salt thereof according to item 68, wherein L⁴ is one of the following isomeric structures:

[Item 70]

The compound or the pharmaceutically acceptable salt thereof according to item 68 or 69, wherein L⁴ is

[Item 71]

The compound or the pharmaceutically acceptable salt thereof according to item 68 or 69, wherein L⁴ is

[Item 72]

The compound or the pharmaceutically acceptable salt thereof according to item 68 or 69, wherein L⁴ is

[Item 73]

The compound or the pharmaceutically acceptable salt thereof according to item 68 or 69, wherein L⁴ is

[Item 74]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 3, 11 to 36, and 66 to 73, wherein R⁵ is a hydrogen atom, an optionally substituted C₁₋₆ alkyl group, an optionally substituted C₃₋₁₀ alicyclic group, an optionally substituted 4- to 10-membered non-aryl heterocycle, optionally substituted C₆₋₁₀ aryl, optionally substituted 5- or 6-membered heteroaryl, an optionally substituted C₁₋₆ alkylthio group, or —NR^(e1)OH, wherein R^(e1) is a hydrogen atom or an optionally substituted C₁₋₆ alkyl group.

[Item 75]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 3, 11 to 36, and 66 to 74, wherein R⁵ is optionally substituted 5- or 6-membered heteroaryl or optionally substituted C₆₋₁₀ aryl.

[Item 76]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 3, 11 to 36, and 66 to 75, wherein R⁵ is optionally substituted 5- or 6-membered heteroaryl.

[Item 77]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 3, 11 to 36, and 66 to 76, wherein R⁵ is an optionally substituted C₄₋₁₀ alicyclic group or an optionally substituted 4- to 10-membered non-aryl heterocycle.

[Item 78]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 3, 11 to 36, and 66 to 74, wherein L⁴ is a single bond and R⁵ is —NR^(e1)OH, wherein R^(e1) is a hydrogen atom or an optionally substituted C₁₋₆ alkyl group.

[Item 79]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 3 and 11 to 36, wherein

L⁴ is

1) —(CH₂)_(p)—CR¹⁰(NHR¹¹)—, 2) —(CH₂)_(q)—CR¹²R¹³—, or 3) —(CH₂)_(p)—CR¹⁰(NHR¹¹)—(CH₂)_(q)—CR¹²R¹³— (wherein p and q are independently 0 or 1),

R¹⁰ is

1) a hydrogen atom, 2) a carboxyl group, or 3) —C(═O)NR^(10a)R^(10b),

R¹⁰ is

1) a hydrogen atom,

2) —C(═O)R a, or

3) an optionally substituted 5- or 6-membered non-aryl heterocyclyl carbonyl group, wherein if R¹⁰ is —C(═O)NR^(10a)R^(10b), R^(10b) and R¹¹ together may form —CH₂CH₂—,

R¹² is

1) a hydrogen atom, or 2) an optionally substituted C₁₋₄ alkyl group,

R¹³ is

1) a hydrogen atom, 2) a hydroxyl group 3) an optionally substituted C₁₋₄ alkyl group 4) a sulfanyl group, 5) a carboxyl group, 6) an optionally substituted C₁₋₄ alkylthio group, 7) —NR^(13a)R^(13b), 8) —NR^(13a)—C(═O)R^(13b), 9) an optionally substituted 5- or 6-membered non-aryl heterocyclyl carbonylamino group, 10) —NR^(13a)—C(═O)NR^(13b)R^(13c), 11) —C(═O)NR^(13a)R^(13b), 12) —C(═O)NR^(13a)OR^(13b), 13) —S(═O)₂—R^(13a), 14) —S(═O)₂—NR^(13a)R^(13b), 15) —C(═O)NR^(13a)—S(═O)₂—R^(13b), or 16) —C(═O)NR^(13a)—S(═O)₂—NR^(13b)R^(13c), and

R^(10a), R^(10b), R^(11a), R^(13a), R^(13b), and R^(13c) are each independently a hydrogen atom or an optionally substituted C₁₋₄ alkyl group.

[Item 80]

The compound or the pharmaceutically acceptable salt thereof according to item 79, wherein R⁵ is a hydrogen atom or an optionally substituted C₁₋₄ alkyl group.

[Item 81]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 3, 11 to 36, and 66 to 76, wherein

R⁵ is selected from the group consisting of

subscript d is the number of substitutable positions on a ring of R⁵,

each R^(6a) is independently selected from the group consisting of

1) a hydrogen atom, 2) a hydroxyl group, 3) a cyano group, 4) a nitro group, 5) halogen, 6) a C₁₋₄ alkyl group, 7) a C₃₋₁₀ alicyclic group, 8) a C₁₋₄ alkoxy group, 9) a C₃₋₁₀ alicyclic oxy group, 10) a C₆₋₁₀ aryloxy group, 11) a 5- or 6-membered heteroaryloxy group, 12) a 4- to 10-membered non-aryl heterocyclyl oxy group, (wherein each substituent from 6) to 12) is optionally substituted), 13) —SO₂—NR^(e2)R^(f2), 14) —NR^(g2)—CR^(e2)(═NR^(f2)), 15) —NR^(g2)—CR^(e2)(═N—OR^(f2)), 16) —NR^(h2)—C(═NR^(g2))NR^(e2)R^(f2), 17) —NR^(h2)—C(═N—OR^(g2))NR^(e2)R^(f2), 18) —NR^(i2)—C(═NR^(h2))NR^(g2)—NR^(e2)R^(f2), 19) —NR^(i2)—C(═N—OR^(h2))NR^(g2)—NR^(e2)R^(f2), 20) —C(═NR^(e2))R^(f2), 21) —C(═N—OR^(e2))R^(f2), 22) —C(═NR^(h2))—NR^(e2)R^(f2), 23) —C(═NR^(h2))NR^(g2)—NR^(e2)R^(f2), 24) —C(═N—OR^(h2))NR^(g2)—NR^(e2)R^(f2), 25) —NR^(e2)R^(f2), 26) —NR^(g2)—NR^(e2)R^(f2), 27) —NR^(e2)OR^(f2), 28) —NR^(e2)—C(═O)R^(f2), 29) —C(═O)NR^(e2)R^(f2), 30) —C(═O)NR^(e2)OR^(f2), 31) —C(═O)NR^(g2)—NR^(e2)R^(f2),

32) —C(═O)R^(e2), 33) —C(═O)OR^(e2), and

34) —C(═N—OR^(h2))NR^(e2)R^(f2), and

each R^(6b) is independently selected from the group consisting of

1) a hydrogen atom, 2) a hydroxyl group, 3) a C₁₋₄ alkyl group (wherein the alkyl group is optionally substituted), 4) a C₃₋₁₀ alicyclic group (wherein the alicyclic group is optionally substituted), 5) —C(═NR^(e2))R^(f2), 6) —C(═N—OR^(e2))R^(f2), 7) —SO₂—NR^(e2)R^(f2), 8) —C(═NR^(h2))—NR^(e2)R^(f2), 9) —C(═NR^(h2))—NR^(e2)R^(f2), 10) —C(═N—OR^(h2))NR^(g2)—NR^(e2)R^(f2), 11) —C(═O)NR^(e2)R^(f2), 12) —C(═O)NR^(e2)OR^(f2), 13) —C(═O)NR^(g2)—NR^(e2)R^(f2),

14) —C(═O)R^(e2), and

15) —C(═N—OR^(h2))NR^(e2)R^(f2).

[Item 82]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 3, 11 to 36, 66 to 76, and 81, wherein

R⁵ is 5- or 6-membered aryl or heteroaryl selected from the group consisting of

subscript d is the number of substitutable positions on a ring of R⁵,

each R^(6a) is independently selected from the group consisting of

1) a hydrogen atom, 2) a hydroxyl group, 3) halogen, 4) a C₁₋₄ alkyl group (wherein the alkyl group is optionally substituted with NR^(e2)R^(f2), a 5- or 6-membered non-aryl heterocycle, —C(═O)OR^(f2), or a hydroxyl group), 5) a C₁₋₄ alkoxy group 6) —NR^(e2)R^(f2), and

7) —C(═O)OR^(e2), and

each R^(6b) is independently selected from the group consisting of

1) a hydrogen atom, 2) a hydroxyl group, and 3) a C₁₋₄ alkyl group (wherein the alkyl group is optionally substituted with NR^(e2)R^(f2), —C(═O)NR^(e2)R^(f2), —C(═O)OR^(f2), or a hydroxyl group).

[Item 83]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 3, 11 to 36, 66 to 76, and 81 to 82, wherein R⁵ is

[Item 84]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 3, 11 to 36, 66 to 76, and 81 to 82, wherein R^(e2) and R^(f2) are the same or different, each independently a hydrogen atom, an optionally substituted C₁₋₆ alkyl group, or an optionally substituted C₃₋₁₀ alicyclic group.

[Item 85]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 3, 11 to 36, 66 to 76, 81 to 82, and 84, wherein R^(e2) and R^(f2) are the same or different, each independently a hydrogen atom or an optionally substituted C₁₋₆ alkyl group.

[Item 86]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 3, 11 to 36, 66 to 76, 81 to 82, and 84 to 85, wherein R^(e2) and R^(f2) are hydrogen atoms.

[Item 87]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 81 to 82 and 84 to 85, wherein R⁶, is —NR^(e2)R^(f2), and one of R^(e2) and R^(f2) is a hydrogen atom and the other is a C₁₋₄ alkyl group (wherein the alkyl group is optionally substituted with an amino group or a hydroxyl group).

[Item 88]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 3, 11 to 36, 66 to 74, and 77, wherein

R⁵ is a 4- to 6-membered non-aryl heterocycle selected from the group consisting of

subscript d is the number of substitutable positions on a ring of R⁵,

each R⁷ is independently selected from the group consisting of

1) a hydrogen atom, 2) a hydroxyl group, 3) a cyano group, 4) halogen, 5) a C₁₋₄ alkyl group, 6) a C₃₋₁₀ alicyclic group, 7) a C₁₋₄ alkoxy group, 8) a C₃₋₁₀ alicyclic oxy group, 9) a C₆₋₁₀ aryloxy group, 10) a 5- or 6-membered heteroaryloxy group, 11) a 4- to 10-membered non-aryl heterocyclyl oxy group, (wherein each substituent from 5) and 11) is optionally substituted), 12) —SO₂—NR^(e3)R^(f3), 13) —NR^(g2)—CR^(e3)(═NR^(f3)), 14) —NR^(g2)—CR^(e3)(═N—OR^(f3)), 15) —NR^(h2)—C(═NR^(g2))NR^(e3)R^(f3), 16) —NR^(h2)—C(═N—OR^(g2))NR^(e3)R^(f3), 17) —NR^(i2)—C(═NR^(h2))NR^(g2)—NR^(e3)R^(f3), 18) —NR^(i2)—C(═N—OR^(h2))NR^(g2)—NR^(e3)R^(f3), 19) —C(═NR^(e3))R^(f3), 20) —C(═N—OR^(e3))R^(f3), 21) —C(═NR^(h2))—NR^(e3)R^(f3), 22) —C(═NR^(h2))NR^(g2)—NR^(e3)R^(f3), 23) —C(═N—OR^(h2))NR^(g2)—NR^(e3)R^(f3), 24) —NR^(e3)R^(f3), 25) —NR^(g2)—NR^(e3)R^(f3), 26) —NR^(e3)OR^(f3), 27) —NR^(e3)—C(═O)R^(f3), 28) —C(═O)NR^(e3)R^(f3), 29) —C(═O)NR^(e3)OR^(f3), 30) —C(═O)NR^(g2)—NR^(e3)R^(f3),

31) —C(═O)R^(e3), 32) —C(═O)OR^(e3), and

33) —C(═N—OR^(h2))NR^(e3)R^(f3),

each R^(7b) is independently selected from the group consisting of

1) a hydrogen atom, 2) a hydroxyl group, 3) a C₁₋₄ alkyl group (wherein the alkyl group is optionally substituted), 4) a C₃₋₁₀ alicyclic group (wherein the alicyclic group is optionally substituted), 5) —C(═NR^(e3))R^(f3), 6) —C(═N—OR^(e3))R^(f3), 7) —SO₂—NR^(e3)R^(f3), 8) —C(═NR^(h2))NR^(e3)R^(f3), 9) —C(═NR^(h2))—NR^(g2)—NR^(e3)R^(f3), 10) —C(═N—OR^(h2))NR^(g2)—NR^(e3)R^(f3), 11) —C(═O)NR^(e3)R^(f3), 12) —C(═O)NR^(e3)OR^(f3), 13) —C(═O)NR^(g2)—NR^(e3)R^(f3),

14) —C(═O)R^(e3), and

15) —C(═N—OR^(h2))NR^(e3)R^(f3), and

R^(e3), R^(f3), R^(g2), R^(h2), and R^(i2) are defined the same as R^(e2), R^(f2), R^(g2), R^(h2), and R^(i2) according to item 3.

[Item 89]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 3, 11 to 36, 66 to 74, 77, and 88, wherein

R⁵ is a 4- to 6-membered non-aryl heterocycle selected from the group consisting of

subscript d is the number of substitutable positions on a ring of R⁵,

each R^(7a) is independently selected from the group consisting of

1) a hydrogen atom, 2) a hydroxyl group, 3) halogen, 4) a C₁₋₄ alkyl group (wherein the alkyl group is optionally substituted with NR^(e3)R^(f3), a 5- or 6-membered non-aryl heterocycle, —C(═O)OR^(f3), or a hydroxyl group), 5) a C₁₋₄ alkoxy group 6) —NR^(e3)R^(f3),

7) —C(═O)OR^(e3),

8) C₆₋₁₀ aryl, and 9) —C(═O)NR^(e3)R^(f3),

each R^(7b) is independently selected from the group consisting of

1) a hydrogen atom, 2) a hydroxyl group, and 3) a C₁₋₄ alkyl group (wherein the alkyl group is optionally substituted with NR^(e3)R^(f3), —C(═O)OR³, or a hydroxyl group), and

R^(e3) and R^(f3) are defined the same as R^(e2) and R^(f2) according to any of items 84 to 86.

[Item 90]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 3, 11 to 36, 66 to 74, and 77, wherein

R⁵ is C₄₋₆ cycloalkyl selected from the group consisting of

subscript d is the number of substitutable positions on a ring of R⁵,

each R^(9a) is independently selected from the group consisting of

1) a hydrogen atom, 2) a hydroxyl group, 3) a cyano group, 4) halogen, 5) a C₁₋₄ alkyl group, 6) a C₃₋₁₀ alicyclic group, 7) a C₁₋₄ alkoxy group, 8) a C₃₋₁₀ alicyclic oxy group, 9) a C₆₋₁₀ aryloxy group, 10) a 5- or 6-membered heteroaryloxy group, 11) a 4- to 10-membered non-aryl heterocyclyl oxy group, (wherein each substituent from 5) and 11) is optionally substituted), 12) —SO₂—NR^(e3)R^(f3), 13) —NR^(g2)—CR^(e3)(═NR^(f3)) 14) —NR^(g2)—CR^(e3)(═N—OR^(f3)), 15) —NR^(h2)—C(═NR^(g2))NR^(e3)R^(f3), 16) —NR^(h2)—C(═N—OR^(g2))NR^(e3)R^(f3), 17) —NR^(i2)—C(═NR^(h2))NR^(g2)—NR^(e3)R^(f3), 18) —NR^(i2)—C(═N—OR^(h2))NR^(g2)—NR^(e3)R^(f3), 19) —C(═NR^(e3))R^(f3), 20) —C(═N—OR^(e3))R^(f3), 21) —C(═NR^(h2))—NR^(e3)R^(f3), 22) —C(═NR^(h2))NR^(g2)—NR^(e3)R^(f3), 23) —C(═N—OR^(h2))NR^(g2)—NR^(e3)R^(f3), 24) —NR^(e3)R^(f3), 25) —NR^(g2)—NR^(e3)R^(f3), 26) —NR^(e3)OR^(f3), 27) —NR^(e3)—C(═O)R^(f3), 28) —C(═O)NR^(e3)R^(f3), 29) —C(═O)NR^(e3)OR^(f3), 30) —C(═O)NR^(g2)—NR^(e3)R^(f3),

31) —C(═O)R^(e3), 32) —C(═O)OR^(e3), and

33) —C(═N—OR^(h2))NR^(e3)R^(f3), and

R^(e3), R^(f3), R^(g2), R^(h2), and R^(i2) are defined the same as R^(e2) and R^(f2) according to item 3.

[Item 91]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 3, 11 to 36, 66 to 74, 77, and 90, wherein

R⁵ is C₄₋₆ cycloalkyl selected from the group consisting of

subscript d is the number of substitutable positions on a ring of R⁵,

each R⁹ is independently selected from the group consisting of

1) a hydrogen atom, 2) a hydroxyl group, 3) halogen, 4) a C₁₋₄ alkyl group (wherein the alkyl group is optionally substituted with NR^(e3)R^(f3), a 5- or 6-membered non-aryl heterocycle, —C(═O)OR^(f3), or a hydroxyl group), 5) a C₁₋₄ alkoxy group 6) —NR^(e3)R^(f3),

7) —C(═O)OR^(e3),

8) C₆₋₁₀ aryl, and 9) —C(═O)NR^(e3)R^(f3), and

R^(e3) and R^(f3) are defined the same as R^(e2) and R^(f2) according to any of items 75 to 77.

[Item 92]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 3, 11 to 36, and 79 to 80, wherein

L⁴ is —CH(NH₂)—CHR¹³—, wherein carbon that attaches to the NH₂ attaches to L³,

R⁵ is a hydrogen atom, and

R¹³ is

1) —NH—C(═O)CH₃, 2) —NH—C(═O)NH₂,

3) —NH—C(═O)CH(NH₂)—CH₂C(═O)NH₂, 4) —NH—C(═O) CH₂—NH₂, 5) —NH—C(═O)CH(NH₂)—CH₂OH, or 6) a pyrrolidin-2-ylcarbonylamino group.

[Item 93]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 3, 11 to 36, and 79 to 80, wherein L⁴ is —CH(NH₂)—CR²R³—, wherein carbon that attaches to the NH₂ attaches to L³,

R⁵ is a hydrogen atom or methyl,

R¹² is a hydrogen atom or methyl, and

R¹³ is a benzylthio group or a sulfanyl group.

[Item 94]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 3, 11 to 36, and 79 to 80, wherein

L⁴ is —CH(NH₂)—(CH₂)_(q)—CHR¹³—, wherein q is 0 or 1, and carbon that attaches to the NH₂ attaches to L³,

R⁵ is a hydrogen atom, and

R¹³ is

1) a carboxyl group,

2) —C(═O)NH₂, 3) —C(═O)NH(CH₃),

4) —C(═O)N(CH₃)₂, 5) —C(═O)NH—(CH₂)₂—OH, 6) —C(═O)NH—(CH₂)₂—NH₂, 7) —C(═O)NH—S(═O)₂—CH₃,

8) —C(═O)NHOH,

9) —S(═O)₂—NH₂, 10) —S(═O)₂—CH₃, or 11) a hydroxyl group.

[Item 95]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 3, 11 to 36, and 79 to 80, wherein

L⁴ is —CH(NHR¹¹)—CH₂—, wherein carbon that attaches to the NHR¹¹ attaches to L³,

R⁵ is hydrogen, and

R¹¹ is

1) —C(═O)CH(NH₂)—CH₂C(═O)NH₂, 2) —C(═O)CH₂—NH₂, 3) —C(═O)CH(CH₃)—NH₂, 4) —C(═O)CH(NH₂)—CH₂OH, or 5) pyrrolidin-2-ylcarbonyl.

[Item 96]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 3, 11 to 36, and 79 to 80, wherein

L⁴ is —CH(NHR¹¹)—CH(COOH)—, wherein carbon that attaches to the NHR¹¹ attaches to L³,

R⁵ is hydrogen, and

R¹¹ is

1) —C(═O)CH(NH₂)—CH₂C(═O)NH₂, 2) —C(═O)CH₂—NH₂, 3) —C(═O)CH(CH₃)—NH₂, 4) —C(═O)CH(NH₂)—CH₂OH, or 5) pyrrolidin-2-ylcarbonyl.

[Item 97]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 3, 11 to 36, and 79 to 80, wherein

L⁴ is —CHR¹³— or —CH₂—CHR¹³—,

R⁵ is hydrogen, and

R¹³ is —C(═O)NH₂ or —C(═O)NHOH.

[Item 98]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 3, 11 to 36, and 79 to 80, wherein

L⁴ is —CH₂—CR¹⁰(NH₂)—, wherein the CH₂ group attaches to L³,

R⁵ is hydrogen, and

R¹⁰ is a carboxy group or —C(═O)NH₂.

[Item 99]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 3, 11 to 36, and 79 to 80, wherein

L⁴ is —(CH₂)_(p)—CR¹⁰(NHR¹¹)—(CH₂)_(q)—CHR¹³— or —CHR¹³—(CH₂)_(q)—CR¹⁰(NHR¹¹)—(CH₂)_(p)—, wherein q is 0 or 1,

R⁵ is hydrogen,

(1) if L⁴ is —CHR³—(CH₂)_(q)—CR¹⁰(NHR¹¹)—(CH₂)_(p)—, carbon of the —CHR¹³— group attaches to L³,

p is 0,

R¹⁰ is a hydrogen atom, a carboxyl group, or —C(═O)NHR^(10b),

R¹¹ is a hydrogen atom,

R^(10b) is a hydrogen atom,

wherein if R¹⁰ is —C(═O)NHR^(10b), R^(10b) and R¹¹ together may form —CH₂CH₂—, and

R¹³ is a hydrogen atom,

(2) if L⁴ is —(CH₂)_(p)—CR¹⁰(NHR¹¹)—(CH₂)_(q)—CHR¹³, carbon of the —(CH₂)_(p)— group attaches to L³,

p is 1,

R¹⁰ and R¹¹ are both hydrogen atoms,

R¹³ is a carboxyl group or —C(═O)NR^(13a)R^(13b), and

R^(13a) and R^(13b) are each independently a hydrogen atom or an optionally substituted C₁₋₄ alkyl group.

[Item 100]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 3, 11 to 36, and 79 to 80, wherein

L⁴ is —CR² (NH₂)—,

R¹² is a hydrogen atom or a methyl group, and

R⁵ is a C₁₋₄ alkyl group optionally substituted with a hydroxyl group.

[Item 101]

The compound or the pharmaceutically acceptable salt thereof according to item 1 or 2, selected from the group consisting of the compounds represented by the following names or structural formulas:

-   5-({1-[amino(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   9-[1-[2-amino-2-(1H-imidazol-4-yl)acetyl]azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   (1aS,7bR)-5-({1-[(2R)-2-amino-2-(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-9-[1-[(2R)-2-amino-2-(1H-imidazol-4-yl)acetyl]azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   (1aS,7bR)-5-({1-[(2S)-2-amino-2-(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-9-[1-[(2S)-2-amino-2-(1H-imidazol-4-yl)acetyl]azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   (1aR,7bS)-5-({1-[(2R)-2-amino-2-(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-9-[1-[(2R)-2-amino-2-(1H-imidazol-4-yl)acetyl]azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   (1aR,7bS)-5-({1-[(2S)-2-amino-2-(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-9-[1-[(2S)-2-amino-2-(1H-imidazol-4-yl)acetyl]azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   5-({1-(2-amino-2-carboxypropyl)azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   9-[1-(propyl     2-amino-2-carboxylate)azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

-   (1aS,7bR)-5-({1-[(2R)-2-amino-2-carboxypropyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-9-[1-[propyl     (2R)-2-amino-2-carboxylate]azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

-   (1aR,7bS)-5-({1-[(2R)-2-amino-2-carboxypropyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-9-[1-[propyl     (2R)-2-amino-2-carboxylate]azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

-   5-({1-[2-amino-2-(1H-imidazol-4-yl)propanoyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   9-[1-[2-amino-2-(1H-imidazol-4-yl)propanoyl]azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   (1aS,7bR)-5-({1-[(2R)-2-amino-2-(1H-imidazol-4-yl)propanoyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-9-[1-[(2R)-2-amino-2-(1H-imidazol-4-yl)propanoyl]azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   (1aS,7bR)-5-({1-[(2S)-2-amino-2-(1H-imidazol-4-yl)propanoyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-9-[1-[(2S)-2-amino-2-(1H-imidazol-4-yl)propanoyl]azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   (1aR,7bS)-5-({1-[(2R)-2-amino-2-(1H-imidazol-4-yl)propanoyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-9-[1-[(2R)-2-amino-2-(1H-imidazol-4-yl)propanoyl]azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   (1aR,7bS)-5-({1-[(2S)-2-amino-2-(1H-imidazol-4-yl)propanoyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

and

-   (2S,4R)-9-[1-[(2S)-2-amino-2-(1H-imidazol-4-yl)propanoyl]azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

[Item 102]

The compound or the pharmaceutically acceptable salt thereof according to item 1 or 2, selected from the group consisting of the compounds represented by the following names or structural formulas:

-   2-hydroxy-5-({1-[(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy)-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   5,5-dihydroxy-9-{1-[(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   (1aS,7bR)-2-hydroxy-5-({1-[(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy)-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-5,5-dihydroxy-9-{1-[(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   (1aR,7bS)-2-hydroxy-5-({1-[(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy)-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-5,5-dihydroxy-9-{1-[(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   2-hydroxy-5-[(1-serylazetidin-3-yl)oxy]-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   5,5-dihydroxy-9-(1-serylazetidin-3-yl)oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   (1aS,7bR)-2-hydroxy-5-[(1-D-serylazetidin-3-yl)oxy]-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-5,5-dihydroxy-9-(1-D-serylazetidin-3-yl)oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   (1aS,7bR)-2-hydroxy-5-[(1-L-serylazetidin-3-yl)oxy]-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-5,5-dihydroxy-9-(1-L-serylazetidin-3-yl)oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   (1aR,7bS)-2-hydroxy-5-[(1-D-serylazetidin-3-yl)oxy]-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-5,5-dihydroxy-9-(1-D-serylazetidin-3-yl)oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   (1aR,7bS)-2-hydroxy-5-[(1-L-serylazetidin-3-yl)oxy]-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-5,5-dihydroxy-9-(1-L-serylazetidin-3-yl)oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   2-hydroxy-5-({1-[4-hydroxy-prolyl]azetidin-3-yl}oxy)-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   5,5-dihydroxy-9-{1-[4-hydroxy-prolyl]azetidin-3-yl}oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   (1aS,7bR)-2-hydroxy-5-({1-[(4R)-4-hydroxy-L-prolyl]azetidin-3-yl}oxy)-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-5,5-dihydroxy-9-{1-[(4R)-4-hydroxy-L-prolyl]azetidin-3-yl}oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   (1aS,7bR)-2-hydroxy-5-({1-[(4S)-4-hydroxy-L-prolyl]azetidin-3-yl}oxy)-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-5,5-dihydroxy-9-{1-[(4S)-4-hydroxy-L-prolyl]azetidin-3-yl}oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   (1aS,7bR)-2-hydroxy-5-({1-[(4R)-4-hydroxy-D-prolyl]azetidin-3-yl}oxy)-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-5,5-dihydroxy-9-{1-[(4R)-4-hydroxy-D-prolyl]azetidin-3-yl}oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   (1aS,7bR)-2-hydroxy-5-({1-[(4S)-4-hydroxy-D-prolyl]azetidin-3-yl}oxy)-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-5,5-dihydroxy-9-{1-[(4S)-4-hydroxy-D-prolyl]azetidin-3-yl}oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   (1aR,7bS)-2-hydroxy-5-({1-[(4R)-4-hydroxy-L-prolyl]azetidin-3-yl}oxy)-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-5,5-dihydroxy-9-{1-[(4R)-4-hydroxy-L-prolyl]azetidin-3-yl}oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   (1aR,7bS)-2-hydroxy-5-({1-[(4S)-4-hydroxy-L-prolyl]azetidin-3-yl}oxy)-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-5,5-dihydroxy-9-{1-[(4S)-4-hydroxy-L-prolyl]azetidin-3-yl}oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   (1aS,7bR)-2-hydroxy-5-({1-[(4R)-4-hydroxy-D-prolyl]azetidin-3-yl}oxy)-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-5,5-dihydroxy-9-{1-[(4R)-4-hydroxy-D-prolyl]azetidin-3-yl}oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   (1aR,7bS)-2-hydroxy-5-({1-[(4S)-4-hydroxy-D-prolyl]azetidin-3-yl}oxy)-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-5,5-dihydroxy-9-{1-[(4S)-4-hydroxy-D-prolyl]azetidin-3-yl}oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   2-hydroxy-5-{[1-(2-methyl-seryl)azetidin-3-yl]oxy}-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   5,5-dihydroxy-9-[1-(2-methyl-seryl)azetidin-3-yl]oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   (1aS,7bR)-2-hydroxy-5-{[1-(2-methyl-D-seryl)azetidin-3-yl]oxy}-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-5,5-dihydroxy-9-[1-(2-methyl-D-seryl)azetidin-3-yl]oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   (1aS,7bR)-2-hydroxy-5-{[1-(2-methyl-L-seryl)azetidin-3-yl]oxy}-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-5,5-dihydroxy-9-[1-(2-methyl-L-seryl)azetidin-3-yl]oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   (1aR,7bS)-2-hydroxy-5-{[1-(2-methyl-D-seryl)azetidin-3-yl]oxy}-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-5,5-dihydroxy-9-[1-(2-methyl-D-seryl)azetidin-3-yl]oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   (1aR,7bS)-2-hydroxy-5-{[1-(2-methyl-L-seryl)azetidin-3-yl]oxy}-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-5,5-dihydroxy-9-[1-(2-methyl-L-seryl)azetidin-3-yl]oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   2-hydroxy-5-[(1-{[morpholin-2-yl]acetyl}azetidin-3-yl)oxy]-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   5,5-dihydroxy-9-(1-{[morpholin-2-yl]acetyl}azetidin-3-yl)oxy-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   (1aS,7bR)-2-hydroxy-5-[(1-{[(2R)-morpholin-2-yl]acetyl}azetidin-3-yl)oxy]-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-5,5-dihydroxy-9-(1-{[(2R)-morpholin-2-yl]acetyl}azetidin-3-yl)oxy-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   (1aS,7bR)-2-hydroxy-5-[(1-{[(2S)-morpholin-2-yl]acetyl}azetidin-3-yl)oxy]-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-5,5-dihydroxy-9-(1-{[(2R)-morpholin-2-yl]acetyl}azetidin-3-yl)oxy-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   (1aR,7bS)-2-hydroxy-5-[(1-{[(2R)-morpholin-2-yl]acetyl}azetidin-3-yl)oxy]-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-5,5-dihydroxy-9-(1-{[(2R)-morpholin-2-yl]acetyl}azetidin-3-yl)oxy-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   (1aR,7bS)-2-hydroxy-5-[(1-{[(2S)-morpholin-2-yl]acetyl}azetidin-3-yl)oxy]-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-5,5-dihydroxy-9-(1-{[(2S)-morpholin-2-yl]acetyl}azetidin-3-yl)oxy-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   (1aS,7bR)-5-({1-[(2S)-2-amino-2-carboxypropyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-9-[1-[propyl     (2S)-2-amino-2-carboxylate]azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

-   (1aR,7bS)-5-({1-[(2S)-2-amino-2-carboxypropyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-9-[1-[propyl     (2S)-2-amino-2-carboxylate]azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

-   5-({1-[2-amino-2-carboxypropyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   9-(1-{2-amino-3-[(2-hydroxyethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

-   (1aS,7bR)-5-[(1-{(2R)-2-amino-3-[(2-hydroxyethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-9-(1-{(2R)-2-amino-3-[(2-hydroxyethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

-   (1aS,7bR)-5-[(1-{(2S)-2-amino-3-[(2-hydroxyethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-9-(1-{(2S)-2-amino-3-[(2-hydroxyethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

-   (1aR,7bS)-5-[(1-{(2R)-2-amino-3-[(2-hydroxyethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-9-(1-{(2R)-2-amino-3-[(2-hydroxyethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

-   (1aR,7bS)-5-[(1-{(2S)-2-amino-3-[(2-hydroxyethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-9-(1-{(2S)-2-amino-3-[(2-hydroxyethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

-   5-[(1-{2-amino-3-[(2-amino-2-oxoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   9-(1-{2-amino-3-[(2-amino-2-oxoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

-   (1aS,7bR)-5-[(1-{(2R)-2-amino-3-[(2-amino-2-oxoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-9-(1-{(2R)-2-amino-3-[(2-amino-2-oxoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

-   (1aS,7bR)-5-[(1-{(2S)-2-amino-3-[(2-amino-2-oxoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-9-(1-{(2S)-2-amino-3-[(2-amino-2-oxoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

-   (1aR,7bS)-5-[(1-{(2R)-2-amino-3-[(2-amino-2-oxoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-9-(1-{(2R)-2-amino-3-[(2-amino-2-oxoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

-   (1aR,7bS)-5-[(1-{(2S)-2-amino-3-[(2-amino-2-oxoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-9-(1-{(2S)-2-amino-3-[(2-amino-2-oxoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

-   5-({1-[5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   9-{1-[5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

-   (1aS,7bR)-5-({1-[(3S,5S)-5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-9-{1-[(3S,5S)-5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

-   (1aS,7bR)-5-({1-[(3R,5S)-5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-9-{1-[(3R,5S)-5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

-   (1aS,7bR)-5-({1-[(3S,5R)-5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-9-{1-[(3S,5R)-5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

-   (1aS,7bR)-5-({1-[(3R,5R)-5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-9-{1-[(3R,5R)-5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

-   (1aR,7bS)-5-({1-[(3S,5S)-5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-9-{1-[(3S,5S)-5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

-   (1aR,7bS)-5-({1-[(3R,5S)-5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-9-{1-[(3R,5S)-5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

-   (1aR,7bS)-5-({1-[(3S,5R)-5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-9-{1-[(3S,5R)-5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

-   (1aR,7bS)-5-({1-[(3R,5R)-5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-9-{1-[(3R,5R)-5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

-   5-{[1-(2-amino-2-oxoethyl)azetidin-3-yl]oxy}-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   9-[1-(2-amino-2-oxoethyl)azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

-   (1aS,7bR)-5-{[1-(2-amino-2-oxoethyl)azetidin-3-yl]oxy}-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-9-[1-(2-amino-2-oxoethyl)azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

-   (1aR,7bS)-5-{[1-(2-amino-2-oxoethyl)azetidin-3-yl]oxy}-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-9-[1-(2-amino-2-oxoethyl)azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

-   2-hydroxy-5-[(1-{2-[(2-hydroxyethoxy)amino]-2-oxoethyl}azetidin-3-yl)oxy]-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   5,5-dihydroxy-9-(1-{2-[(2-hydroxyethoxy)amino]-2-oxoethyl}azetidin-3-yl)oxy-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   (1aS,7bR)-2-hydroxy-5-[(1-{2-[(2-hydroxyethoxy)amino]-2-oxoethyl}azetidin-3-yl)oxy]-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-5,5-dihydroxy-9-(1-{2-[(2-hydroxyethoxy)amino]-2-oxoethyl}azetidin-3-yl)oxy-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   (1aR,7bS)-2-hydroxy-5-[(1-{2-[(2-hydroxyethoxy)amino]-2-oxoethyl}azetidin-3-yl)oxy]-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-5,5-dihydroxy-9-(1-{2-[(2-hydroxyethoxy)amino]-2-oxoethyl}azetidin-3-yl)oxy-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   5-({1-[2-amino-3-hydroxy-2-(hydroxymethyl)propyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   9-{1-[2-amino-3-hydroxy-2-(hydroxymethyl)propyl]azetidin-3-yl}oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

-   (1aS,7bR)-5-({1-[2-amino-3-hydroxy-2-(hydroxymethyl)propyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-9-{1-[2-amino-3-hydroxy-2-(hydroxymethyl)propyl]azetidin-3-yl}oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

-   (1aR,7bS)-5-({1-[2-amino-3-hydroxy-2-(hydroxymethyl)propyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-9-{1-[2-amino-3-hydroxy-2-(hydroxymethyl)propyl]azetidin-3-yl}oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

-   5-({1-[(1-aminocyclopropyl)methyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   9-{1-[(1-aminocyclopropyl)methyl]azetidin-3-yl}oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

-   (1aS,7bR)-5-({1-[(1-aminocyclopropyl)methyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-9-{1-[(1-aminocyclopropyl)methyl]azetidin-3-yl}oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

-   (1aR,7bS)-5-({1-[(1-aminocyclopropyl)methyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-9-{1-[(1-aminocyclopropyl)methyl]azetidin-3-yl}oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

-   2-hydroxy-5-({1-[(1H-1,2,4-triazol-3-yl)methyl]azetidin-3-yl}oxy)-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   5,5-dihydroxy-9-{1-[(1H-1,2,4-triazol-3-yl)methyl]azetidin-3-yl}oxy-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   (1aS,7bR)-2-hydroxy-5-({1-[(1H-1,2,4-triazol-3-yl)methyl]azetidin-3-yl}oxy)-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-5,5-dihydroxy-9-{1-[(1H-1,2,4-triazol-3-yl)methyl]azetidin-3-yl}oxy-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   (1aR,7bS)-2-hydroxy-5-({1-[(1H-1,2,4-triazol-3-yl)methyl]azetidin-3-yl}oxy)-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-5,5-dihydroxy-9-{1-[(1H-1,2,4-triazol-3-yl)methyl]azetidin-3-yl}oxy-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   5-{[1-({4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy}-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   9-[1-({4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

-   (1aS,7bR)-5-{[1-({(1r,4r)-4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy}-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-9-[1-({(1r,4r)-4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

-   (1aS,7bR)-5-{[1-({(1s,4r)-4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy}-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-9-[1-({(1s,4r)-4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

-   (1aS,7bR)-5-{[1-({(1r,4s)-4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy}-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-9-[1-({(1r,4s)-4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0²′     ]undeca-1(7),8,10-triene-8-carboxylate

-   (1aS,7bR)-5-{[1-({(1s,4s)-4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy}-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-9-[1-({(1s,4s)-4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

-   (1aR,7bS)-5-{[1-({(1r,4r)-4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy}-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-9-[1-({(1r,4r)-4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

-   (1aR,7bS)-5-{[1-({(1s,4r)-4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy}-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-9-[1-({(1s,4r)-4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

-   (1aR,7bS)-5-{[1-({(1r,4s)-4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy}-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-9-[1-({(1r,4s)-4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

-   (1aR,7bS)-5-{[1-({(1s,4s)-4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy}-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-9-[1-({(1s,4s)-4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

-   5-[(1-{2-amino-3-[(2-aminoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   9-(1-{2-amino-3-[(2-aminoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

-   (1aS,7bR)-5-[(1-{(2R)-2-amino-3-[(2-aminoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-9-(1-{(2R)-2-amino-3-[(2-aminoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

-   (1aS,7bR)-5-[(1-{(2S)-2-amino-3-[(2-aminoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-9-(1-{(2S)-2-amino-3-[(2-aminoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

-   (1aR,7bS)-5-[(1-{(2R)-2-amino-3-[(2-aminoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-9-(1-{(2R)-2-amino-3-[(2-aminoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

-   (1aR,7bS)-5-[(1-{(2S)-2-amino-3-[(2-aminoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-9-(1-{(2S)-2-amino-3-[(2-aminoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

-   5-[(1-histidylazetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   9-(1-histidylazetidin-3-yl)oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic     acid

-   (1aS,7bR)-5-[(1-D-histidylazetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-9-(1-D-histidylazetidin-3-yl)oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic     acid

-   (1aS,7bR)-5-[(1-L-histidylazetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-9-(1-L-histidylazetidin-3-yl)oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic     acid

-   (1aR,7bS)-5-[(1-D-histidylazetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-9-(1-D-histidylazetidin-3-yl)oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic     acid

-   (1aR,7bS)-5-[(1-L-histidylazetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-9-(1-L-histidylazetidin-3-yl)oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic     acid

-   5-{[1-(2-aminoethyl)azetidin-3-yl]oxy}-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   9-[1-(2-aminoethyl)azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic     acid

-   (1aS,7bR)-5-{[1-(2-aminoethyl)azetidin-3-yl]oxy}-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-9-[1-(2-aminoethyl)azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic     acid

-   (1aR,7bS)-5-{[1-(2-aminoethyl)azetidin-3-yl]oxy}-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-9-[1-(2-aminoethyl)azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic     acid

-   5-[(1-{[5-(aminomethyl)morpholin-2-yl]acetyl}azetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   9-(1-{[5-(aminomethyl)morpholin-2-yl]acetyl}azetidin-3-yl)oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic     acid

-   (1aS,7bR)-5-[(1-{[5-(aminomethyl)morpholin-2-yl]acetyl}azetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-9-(1-{[5-(aminomethyl)morpholin-2-yl]acetyl}azetidin-3-yl)oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic     acid

-   (1aR,7bS)-5-[(1-{[5-(aminomethyl)morpholin-2-yl]acetyl}azetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-9-(1-{[5-(aminomethyl)morpholin-2-yl]acetyl}azetidin-3-yl)oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic     acid

-   5-({1-[2-amino-2-methyl-3-{[2-(methylamino)-2-oxoethyl]amino}-3-oxopropyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   9-({1-[2-amino-2-methyl-3-{[2-(methylamino)-2-oxoethyl]amino}-3-oxopropyl]azetidin-3-yl}oxy)-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic     acid

-   (1aS,7bR)-5-({1-[(2R)-2-amino-2-methyl-3-{[2-(methylamino)-2-oxoethyl]amino}-3-oxopropyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-9-({1-[(2R)-2-amino-2-methyl-3-{[2-(methylamino)-2-oxoethyl]amino}-3-oxopropyl]azetidin-3-yl}oxy)-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0²′     ]undeca-1(7),8,10-triene-8-carboxylic acid

-   (1aS,7bR)-5-({1-[(2S)-2-amino-2-methyl-3-{[2-(methylamino)-2-oxoethyl]amino}-3-oxopropyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-9-({1-[(2S)-2-amino-2-methyl-3-{[2-(methylamino)-2-oxoethyl]amino}-3-oxopropyl]azetidin-3-yl}oxy)-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic     acid

-   (1aR,7bS)-5-({1-[(2R)-2-amino-2-methyl-3-{[2-(methylamino)-2-oxoethyl]amino}-3-oxopropyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-9-({1-[(2R)-2-amino-2-methyl-3-{[2-(methylamino)-2-oxoethyl]amino}-3-oxopropyl]azetidin-3-yl}oxy)-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic     acid

-   (1aR,7bS)-5-({1-[(2S)-2-amino-2-methyl-3-{[2-(methylamino)-2-oxoethyl]amino}-3-oxopropyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-9-({1-[(2S)-2-amino-2-methyl-3-{[2-(methylamino)-2-oxoethyl]amino}-3-oxopropyl]azetidin-3-yl}oxy)-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic     acid

-   5-({1-[2-amino-3-{[2-(dimethylamino)-2-oxoethyl]amino}-2-methyl-3-oxopropyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   9-({1-[2-amino-3-{[2-(dimethylamino)-2-oxoethyl]amino}-2-methyl-3-oxopropyl]azetidin-3-yl}oxy)-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic     acid

-   (1aS,7bR)-5-({1-[(2R)-2-amino-3-{[2-(dimethylamino)-2-oxoethyl]amino}-2-methyl-3-oxopropyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-9-({1-[(2R)-2-amino-3-{[2-(dimethylamino)-2-oxoethyl]amino}-2-methyl-3-oxopropyl]azetidin-3-yl}oxy)-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic     acid

-   (1aS,7bR)-5-({1-[(2S)-2-amino-3-{[2-(dimethylamino)-2-oxoethyl]amino}-2-methyl-3-oxopropyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-9-({1-[(2S)-2-amino-3-{[2-(dimethylamino)-2-oxoethyl]amino}-2-methyl-3-oxopropyl]azetidin-3-yl}oxy)-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic     acid

-   (1aR,7bS)-5-({1-[(2R)-2-amino-3-{[2-(dimethylamino)-2-oxoethyl]amino}-2-methyl-3-oxopropyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-9-({1-[(2R)-2-amino-3-{[2-(dimethylamino)-2-oxoethyl]amino}-2-methyl-3-oxopropyl]azetidin-3-yl}oxy)-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0²′     ]undeca-1(7),8,10-triene-8-carboxylic acid

-   (1aR,7bS)-5-({1-[(2S)-2-amino-3-{[2-(dimethylamino)-2-oxoethyl]amino}-2-methyl-3-oxopropyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-9-({1-[(2S)-2-amino-3-{[2-(dimethylamino)-2-oxoethyl]amino}-2-methyl-3-oxopropyl]azetidin-3-yl}oxy)-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic     acid

-   2-hydroxy-5-[(1-{[4-methylmorpholin-2-yl]acetyl}azetidin-3-yl)oxy]-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   5,5-dihydroxy-9-[(1-{[(4-methylmorpholin-2-yl]acetyl}azetidin-3-yl)oxy]-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   (1aS,7bR)-2-hydroxy-5-[(1-{[(2R)-4-methylmorpholin-2-yl]acetyl}azetidin-3-yl)oxy]-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-5,5-dihydroxy-9-[(1-{[(2R)-4-methylmorpholin-2-yl]acetyl}azetidin-3-yl)oxy]-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   (1aS,7bR)-2-hydroxy-5-[(1-{[(2S)-4-methylmorpholin-2-yl]acetyl}azetidin-3-yl)oxy]-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-5,5-dihydroxy-9-[(1-{[(2S)-4-methylmorpholin-2-yl]acetyl}azetidin-3-yl)oxy]-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   (1aR,7bS)-2-hydroxy-5-[(1-{[(2R)-4-methylmorpholin-2-yl]acetyl}azetidin-3-yl)oxy]-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-5,5-dihydroxy-9-[(1-{[(2R)-4-methylmorpholin-2-yl]acetyl}azetidin-3-yl)oxy]-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   (1aR,7bS)-2-hydroxy-5-[(1-{[(2S)-4-methylmorpholin-2-yl]acetyl}azetidin-3-yl)oxy]-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-5,5-dihydroxy-9-[(1-{[(2R)-4-methylmorpholin-2-yl]acetyl}azetidin-3-yl)oxy]-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   5-[(1-{[4,4-dimethylmorpholin-4-ium-2-yl]acetyl}azetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylate

-   9-[(1-{[4,4-dimethylmorpholin-4-ium-2-yl]acetyl}azetidin-3-yl)oxy]-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic     acid

-   (1aS,7bR)-5-[(1-{[(2R)-4,4-dimethylmorpholin-4-ium-2-yl]acetyl}azetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylate

-   (2R,4S)-9-[(1-{[(2R)-4,4-dimethylmorpholin-4-ium-2-yl]acetyl}azetidin-3-yl)oxy]-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic     acid

-   (1aS,7bR)-5-[(1-{[(2S)-4,4-dimethylmorpholin-4-ium-2-yl]acetyl}azetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylate

-   (2R,4S)-9-[(1-{[(2S)-4,4-dimethylmorpholin-4-ium-2-yl]acetyl}azetidin-3-yl)oxy]-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic     acid

-   (1aR,7bS)-5-[(1-{[(2R)-4,4-dimethylmorpholin-4-ium-2-yl]acetyl}azetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylate

-   (2S,4R)-9-[(1-{[(2R)-4,4-dimethylmorpholin-4-ium-2-yl]acetyl}azetidin-3-yl)oxy]-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic     acid

-   (1aR,7bS)-5-[(1-{[(2S)-4,4-dimethylmorpholin-4-ium-2-yl]acetyl}azetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylate

-   (2S,4R)-9-[(1-{[(2S)-4,4-dimethylmorpholin-4-ium-2-yl]acetyl}azetidin-3-yl)oxy]-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic     acid

-   (1aR,7bS)-2-hydroxy-5-({1-[(3-hydroxy-2-methyl-4-oxopyridin-1(4H)-yl)acetyl]azetidin-3-yl}oxy)-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   5,5-dihydroxy-9-({1-[(3-hydroxy-2-methyl-4-oxopyridin-1(4H)-yl)acetyl]azetidin-3-yl}oxy)-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   (1aR,7bS)-2-hydroxy-5-({1-[(3-hydroxy-2-methyl-4-oxopyridin-1(4H)-yl)acetyl]azetidin-3-yl}oxy)-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-5,5-dihydroxy-9-({1-[(3-hydroxy-2-methyl-4-oxopyridin-1(4H)-yl)acetyl]azetidin-3-yl}oxy)-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   (1aS,7bR)-2-hydroxy-5-({1-[(3-hydroxy-2-methyl-4-oxopyridin-1(4H)-yl)acetyl]azetidin-3-yl}oxy)-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

and

-   (2R,4S)-5,5-dihydroxy-9-({1-[(3-hydroxy-2-methyl-4-oxopyridin-1(4H)-yl)acetyl]azetidin-3-yl}oxy)-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

[Item 103]

A compound represented by formula (11):

or a pharmaceutically acceptable salt thereof, wherein R^(G) is a hydroxyl group, a thiol group, or —NHR^(a1), R^(a1), X, R¹, R², R³, R⁴, R⁶¹, R⁶², R⁶³, and R⁶⁴ are defined the same as the definition according to any of items 1 to 16, and formula (1a) is defined the same as item 1 or 2.

[Item 104]

The compound or the pharmaceutically acceptable salt thereof according to item 103, wherein the compound of formula (11) is represented by formula (12):

wherein X, R¹, R², R³, and R⁴ are defined the same as the definition according to item 17 or 18.

[Item 105]

The compound or the pharmaceutically acceptable salt thereof according to item 103 or 104, wherein the compound of formula (11) or formula (12) is represented by formula (13):

wherein X, Y, ring A, L³, L⁴, R¹, R², R⁴, and R⁵ are defined the same as the definition according to any of items 19 to 23 and 29 to 32.

[Item 106]

The compound or the pharmaceutically acceptable salt thereof according to item 105, wherein X and R^(G) are hydroxyl groups, R⁴ is a carboxyl group, and ring A is an optionally substituted 4- to 6-membered nitrogen-containing non-aryl heterocycle.

[Item 107]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 103 to 106, wherein the compound of formula (11), formula (12), or formula (13) is represented by formula (14):

wherein X, L³, L⁴, m, n, and R⁵ are defined the same as the definition according to any one of items 33 to 64.

[Item 108]

The compound or the pharmaceutically acceptable salt thereof according to item 107, wherein the compound of formula (14) is one of the enantiomers represented by formula (15):

and formula (16):

wherein X, L³, L⁴, m, n, and R⁵ are defined the same as the definition according to any one of items 33 to 64.

[Item 109]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 103 to 108, wherein R^(G) is a hydroxyl group or a thiol group.

[Item 110]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 103 to 109, wherein R^(G) is a hydroxyl group.

[Item 111]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 103 to 110, wherein X is a hydroxyl group or a C₁₋₆ alkoxy group.

[Item 112]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 103 to 111, wherein X is a hydroxyl group.

[Item 113]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 107 to 112, wherein m is 1 or 2, n is 1 or 2, and m+n is 2 or 3.

[Item 114]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 107 to 113, wherein m is 1, and n is 1.

[Item 115]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 103 to 114, wherein L³ is defined the same as the definition according to item 25 or 26.

[Item 116]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 103 to 115, wherein L⁴ and R⁵ are defined the same as the definition according to any one of items 27 and 66 to 100.

[Item 117]

The compound or the pharmaceutically acceptable salt thereof according to item 104, selected from the group consisting of the compounds represented by the following names or structural formulas:

-   6-({1-[amino(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy)-3-(2-boronocyclopropyl)-2-hydroxybenzoic     acid

-   6-({1-[(2R)-2-amino-2-(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy)-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-({1-[(2S)-2-amino-2-(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy)-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-({1-[(2R)-2-amino-2-(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy)-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-({1-[(2S)-2-amino-2-(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy)-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-({1-(2-amino-2-carboxypropyl)azetidin-3-yl}oxy)-3-(2-boronocyclopropyl)-2-hydroxybenzoic     acid

-   6-({1-[(2R)-2-amino-2-carboxypropyl]azetidin-3-yl}oxy)-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-({1-[(2R)-2-amino-2-carboxypropyl]azetidin-3-yl}oxy)-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-({1-[2-amino-2-(1H-imidazol-4-yl)propanoyl]azetidin-3-yl}oxy)-3-(2-boronocyclopropyl)-2-hydroxybenzoic     acid

-   6-({1-[(2R)-2-amino-2-(1H-imidazol-4-yl)propanoyl]azetidin-3-yl}oxy)-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-({1-[(2S)-2-amino-2-(1H-imidazol-4-yl)propanoyl]azetidin-3-yl}oxy)-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-({1-[(2R)-2-amino-2-(1H-imidazol-4-yl)propanoyl]azetidin-3-yl}oxy)-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

and

-   6-({1-[(2S)-2-amino-2-(1H-imidazol-4-yl)propanoyl]azetidin-3-yl}oxy)-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

[Item 118]

The compound or the pharmaceutically acceptable salt thereof according to item 104, selected from the group consisting of the compounds represented by the following names or structural formulas:

-   2-boronocyclopropyl]-2-hydroxy-6-({1-[(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy)benzoic     acid

-   3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxy-6-({1-[(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy)benzoic     acid

-   3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxy-6-({1-[(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy)benzoic     acid

-   3-[2-boronocyclopropyl]-2-hydroxy-6-[(1-serylazetidin-3-yl)oxy]benzoic     acid

-   3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxy-6-[(1-D-serylazetidin-3-yl)oxy]benzoic     acid

-   3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxy-6-[(1-L-serylazetidin-3-yl)oxy]benzoic     acid

-   3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxy-6-[(1-D-serylazetidin-3-yl)oxy]benzoic     acid

-   3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxy-6-[(1-L-serylazetidin-3-yl)oxy]benzoic     acid

-   3-[2-boronocyclopropyl]-2-hydroxy-6-({1-[4-hydroxy-L-prolyl]azetidin-3-yl}oxy)benzoic     acid

-   3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxy-6-({1-[(4R)-4-hydroxy-L-prolyl]azetidin-3-yl}oxy)benzoic     acid

-   3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxy-6-({1-[(4S)-4-hydroxy-L-prolyl]azetidin-3-yl}oxy)benzoic     acid

-   3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxy-6-({1-[(4R)-4-hydroxy-D-prolyl]azetidin-3-yl}oxy)benzoic     acid

-   3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxy-6-({1-[(4S)-4-hydroxy-D-prolyl]azetidin-3-yl}oxy)benzoic     acid

-   3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxy-6-({1-[(4R)-4-hydroxy-L-prolyl]azetidin-3-yl}oxy)benzoic     acid

-   3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxy-6-({1-[(4S)-4-hydroxy-L-prolyl]azetidin-3-yl}oxy)benzoic     acid

-   3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxy-6-({1-[(4R)-4-hydroxy-D-prolyl]azetidin-3-yl}oxy)benzoic     acid

-   3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxy-6-({1-[(4S)-4-hydroxy-D-prolyl]azetidin-3-yl}oxy)benzoic     acid

-   3-[2-boronocyclopropyl]-2-hydroxy-6-{[1-(2-methyl-seryl)azetidin-3-yl]oxy}benzoic     acid

-   3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxy-6-{[1-(2-methyl-D-seryl)azetidin-3-yl]oxy}benzoic     acid

-   3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxy-6-{[1-(2-methyl-L-seryl)azetidin-3-yl]oxy}benzoic     acid

-   3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxy-6-{[1-(2-methyl-D-seryl)azetidin-3-yl]oxy}benzoic     acid

-   3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxy-6-{[1-(2-methyl-L-seryl)azetidin-3-yl]oxy}benzoic     acid

-   3-[(2-boronocyclopropyl]-2-hydroxy-6-[(1-{[morpholin-2-yl]acetyl}azetidin-3-yl)oxy]benzoic     acid

-   3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxy-6-[(1-{[(2R)-morpholin-2-yl]acetyl}azetidin-3-yl)oxy]benzoic     acid

-   3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxy-6-[(1-{[(2S)-morpholin-2-yl]acetyl}azetidin-3-yl)oxy]benzoic     acid

-   3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxy-6-[(1-{[(2R)-morpholin-2-yl]acetyl}azetidin-3-yl)oxy]benzoic     acid

-   3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxy-6-[(1-{[(2S)-morpholin-2-yl]acetyl}azetidin-3-yl)oxy]benzoic     acid

-   6-({1-[(2S)-2-amino-2-carboxypropyl]azetidin-3-yl}oxy)-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-({1-[(2S)-2-amino-2-carboxypropyl]azetidin-3-yl}oxy)-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-[(1-{2-amino-3-[(2-hydroxyethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-3-[2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-[(1-{(2R)-2-amino-3-[(2-hydroxyethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-[(1-{(2S)-2-amino-3-[(2-hydroxyethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-[(1-{(2R)-2-amino-3-[(2-hydroxyethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-[(1-{(2S)-2-amino-3-[(2-hydroxyethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-[(1-{2-amino-3-[(2-amino-2-oxoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-3-[2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-[(1-{(2R)-2-amino-3-[(2-amino-2-oxoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-[(1-{(2S)-2-amino-3-[(2-amino-2-oxoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-[(1-{(2R)-2-amino-3-[(2-amino-2-oxoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-[(1-{(2S)-2-amino-3-[(2-amino-2-oxoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   3-[2-boronocyclopropyl]-6-({1-[(5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy)-2-hydroxybenzoic     acid

-   3-[(1R,2S)-2-boronocyclopropyl]-6-({1-[(3S,5S)-5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy)-2-hydroxybenzoic     acid

-   3-[(1R,2S)-2-boronocyclopropyl]-6-({1-[(3R,5S)-5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy)-2-hydroxybenzoic     acid

-   3-[(1R,2S)-2-boronocyclopropyl]-6-({1-[(3S,5R)-5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy)-2-hydroxybenzoic     acid

-   3-[(1R,2S)-2-boronocyclopropyl]-6-({1-[(3R,5R)-5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy)-2-hydroxybenzoic     acid

-   3-[(1S,2R)-2-boronocyclopropyl]-6-({1-[(3S,5S)-5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy)-2-hydroxybenzoic     acid

-   3-[(1S,2R)-2-boronocyclopropyl]-6-({1-[(3R,5S)-5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy)-2-hydroxybenzoic     acid

-   3-[(1S,2R)-2-boronocyclopropyl]-6-({1-[(3S,5R)-5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy)-2-hydroxybenzoic     acid

-   3-[(1S,2R)-2-boronocyclopropyl]-6-({1-[(3R,5R)-5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy)-2-hydroxybenzoic     acid

-   6-{[1-(2-amino-2-oxoethyl)azetidin-3-yl]oxy}-3-[2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-{[1-(2-amino-2-oxoethyl)azetidin-3-yl]oxy}-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-{[1-(2-amino-2-oxoethyl)azetidin-3-yl]oxy}-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   3-[(2-boronocyclopropyl]-2-hydroxy-6-[(1-{2-[(2-hydroxyethoxy)amino]-2-oxoethyl}azetidin-3-yl)oxy]benzoic     acid

-   3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxy-6-[(1-{2-[(2-hydroxyethoxy)amino]-2-oxoethyl}azetidin-3-yl)oxy]benzoic     acid

-   3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxy-6-[(1-{2-[(2-hydroxyethoxy)amino]-2-oxoethyl}azetidin-3-yl)oxy]benzoic     acid

-   6-({1-[2-amino-3-hydroxy-2-(hydroxymethyl)propyl]azetidin-3-yl}oxy)-3-[2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-({1-[2-amino-3-hydroxy-2-(hydroxymethyl)propyl]azetidin-3-yl}oxy)-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-({1-[2-amino-3-hydroxy-2-(hydroxymethyl)propyl]azetidin-3-yl}oxy)-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-({1-[(1-aminocyclopropyl)methyl]azetidin-3-yl}oxy)-3-[2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-({1-[(1-aminocyclopropyl)methyl]azetidin-3-yl}oxy)-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-({1-[(1-aminocyclopropyl)methyl]azetidin-3-yl}oxy)-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   3-[2-boronocyclopropyl]-2-hydroxy-6-({1-[(1H-1,2,4-triazol-3-yl)methyl]azetidin-3-yl}oxy)benzoic     acid

-   3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxy-6-({1-[(1H-1,2,4-triazol-3-yl)methyl]azetidin-3-yl}oxy)benzoic     acid

-   3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxy-6-({1-[(1H-1,2,4-triazol-3-yl)methyl]azetidin-3-yl}oxy)benzoic     acid

-   6-{[1-({4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy}-3-[2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-{[1-({(1r,4r)-4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy}-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-{[1-({(1s,4r)-4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy}-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-{[1-({(1r,4s)-4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy}-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-{[1-({(1s,4s)-4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy}-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-{[1-({(1r,4r)-4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy}-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-{[1-({(1s,4r)-4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy}-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-{[1-({(1r,4s)-4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy}-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-{[1-({(1s,4s)-4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy}-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-[(1-{2-amino-3-[(2-aminoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-3-[2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-[(1-{(2R)-2-amino-3-[(2-aminoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-[(1-{(2S)-2-amino-3-[(2-aminoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-[(1-{(2R)-2-amino-3-[(2-aminoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-[(1-{(2S)-2-amino-3-[(2-aminoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   3-(2-boronocyclopropyl)-6-[(1-histidylazetidin-3-yl)oxy]-2-hydroxybenzoic     acid

-   3-[(1R,2S)-2-boronocyclopropyl]-6-[(1-D-histidylazetidin-3-yl)oxy]-2-hydroxybenzoic     acid

-   3-[(1R,2S)-2-boronocyclopropyl]-6-[(1-L-histidylazetidin-3-yl)oxy]-2-hydroxybenzoic     acid

-   3-[(1S,2R)-2-boronocyclopropyl]-6-[(1-D-histidylazetidin-3-yl)oxy]-2-hydroxybenzoic     acid

-   3-[(1S,2R)-2-boronocyclopropyl]-6-[(1-L-histidylazetidin-3-yl)oxy]-2-hydroxybenzoic     acid

-   6-{[1-(2-aminoethyl)azetidin-3-yl]oxy}-3-(2-boronocyclopropyl)-2-hydroxybenzoic     acid

-   6-{[1-(2-aminoethyl)azetidin-3-yl]oxy}-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-{[1-(2-aminoethyl)azetidin-3-yl]oxy}-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-[(1-{[5-(aminomethyl)morpholin-2-yl]acetyl}azetidin-3-yl)oxy]-3-(2-boronocyclopropyl)-2-hydroxybenzoic     acid

-   6-[(1-{[5-(aminomethyl)morpholin-2-yl]acetyl}azetidin-3-yl)oxy]-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-[(1-{[5-(aminomethyl)morpholin-2-yl]acetyl}azetidin-3-yl)oxy]-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-({1-[2-amino-2-methyl-3-{[2-(methylamino)-2-oxoethyl]amino}-3-oxopropyl]azetidin-3-yl}oxy)-3-[2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-({1-[(2R)-2-amino-2-methyl-3-{[2-(methylamino)-2-oxoethyl]amino}-3-oxopropyl]azetidin-3-yl}oxy)-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-({1-[(2S)-2-amino-2-methyl-3-{[2-(methylamino)-2-oxoethyl]amino}-3-oxopropyl]azetidin-3-yl}oxy)-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-({1-[(2R)-2-amino-2-methyl-3-{[2-(methylamino)-2-oxoethyl]amino}-3-oxopropyl]azetidin-3-yl}oxy)-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-({1-[(2S)-2-amino-2-methyl-3-{[2-(methylamino)-2-oxoethyl]amino}-3-oxopropyl]azetidin-3-yl}oxy)-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-({1-[2-amino-3-{[2-(dimethylamino)-2-oxoethyl]amino}-2-methyl-3-oxopropyl]azetidin-3-yl}oxy)-3-[2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-({1-[(2R)-2-amino-3-{[2-(dimethylamino)-2-oxoethyl]amino}-2-methyl-3-oxopropyl]azetidin-3-yl}oxy)-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-({1-[(2S)-2-amino-3-{[2-(dimethylamino)-2-oxoethyl]amino}-2-methyl-3-oxopropyl]azetidin-3-yl}oxy)-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-({1-[(2R)-2-amino-3-{[2-(dimethylamino)-2-oxoethyl]amino}-2-methyl-3-oxopropyl]azetidin-3-yl}oxy)-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-({1-[(2S)-2-amino-3-{[2-(dimethylamino)-2-oxoethyl]amino}-2-methyl-3-oxopropyl]azetidin-3-yl}oxy)-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   3-[2-boronocyclopropyl]-2-hydroxy-6-[(1-{[4-methylmorpholin-2-yl]acetyl}azetidin-3-yl)oxy]benzoic     acid

-   3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxy-6-[(1-{[(2R)-4-methylmorpholin-2-yl]acetyl}azetidin-3-yl)oxy]benzoic     acid

-   3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxy-6-[(1-{[(2S)-4-methylmorpholin-2-yl]acetyl}azetidin-3-yl)oxy]benzoic     acid

-   3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxy-6-[(1-{[(2R)-4-methylmorpholin-2-yl]acetyl}azetidin-3-yl)oxy]benzoic     acid

-   3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxy-6-[(1-{[(2S)-4-methylmorpholin-2-yl]acetyl}azetidin-3-yl)oxy]benzoic     acid

-   3-[2-boronocyclopropyl]-6-[(1-{[4,4-dimethylmorpholin-4-ium-2-yl]acetyl}azetidin-3-yl)oxy]-2-hydroxybenzoate

-   3-[(1R,2S)-2-boronocyclopropyl]-6-[(1-{[(2R)-4,4-dimethylmorpholin-4-ium-2-yl]acetyl}azetidin-3-yl)oxy]-2-hydroxybenzoate

-   3-[(1R,2S)-2-boronocyclopropyl]-6-[(1-{[(2S)-4,4-dimethylmorpholin-4-ium-2-yl]acetyl}azetidin-3-yl)oxy]-2-hydroxybenzoate

-   3-[(1S,2R)-2-boronocyclopropyl]-6-[(1-{[(2R)-4,4-dimethylmorpholin-4-ium-2-yl]acetyl}azetidin-3-yl)oxy]-2-hydroxybenzoate

-   3-[(1S,2R)-2-boronocyclopropyl]-6-[(1-{[(2S)-4,4-dimethylmorpholin-4-ium-2-yl]acetyl}azetidin-3-yl)oxy]-2-hydroxybenzoate

-   3-(2-boronocyclopropyl)-2-hydroxy-6-({1-[(3-hydroxy-2-methyl-4-oxopyridin-1(4H)-yl)acetyl]azetidin-3-yl}oxy)benzoic     acid

-   3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxy-6-({1-[(3-hydroxy-2-methyl-4-oxopyridin-1(4H)-yl)acetyl]azetidin-3-yl}oxy)benzoic     acid

and

-   3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxy-6-({1-[(3-hydroxy-2-methyl-4-oxopyridin-1(4H)-yl)acetyl]azetidin-3-yl}oxy)benzoic     acid

[Item 119]

A medicament comprising the compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to item 118.

[Item 120]

The medicament according to item 119, which is a therapeutic drug or a prophylactic drug for a bacterial infection.

[Item 121]

An agent for inhibiting β-lactamase, comprising the compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 118 as an active ingredient.

[Item 122]

A pharmaceutical composition comprising the compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 118 and a pharmaceutically acceptable carrier.

[Item 123]

The pharmaceutical composition according to item 122, further comprising an additional agent.

[Item 124]

The pharmaceutical composition according to item 123, wherein the additional agent is selected from the group consisting of an antibacterial agent, an antifungal agent, an antiviral agent, an anti-inflammatory agent, and an anti-allergic agent.

[Item 125]

The pharmaceutical composition according to item 123 or 124, wherein the additional agent is a β-lactam agent.

[Item 126]

The pharmaceutical composition according to item 124 or 125, wherein a β-lactam agent, which is the additional agent, is selected from the group consisting of amoxicillin, ampicillin (pivampicillin, hetacillin, bacampicillin, metampicillin, and talampicillin), epicillin, carbenicillin (carindacillin), ticarcillin, temocillin, azlocillin, piperacillin, mezlocillin, mecillinam (pivmecillinam), sulbenicillin, benzylpenicillin (G), clometocillin, benzathine benzylpenicillin, procaine benzylpenicillin, azidocillin, penamecillin, phenoxymethyl penicillin (V), propicillin, benzathine phenoxymethylpenicillin, phenethicillin, cloxacillin (dicloxacillin and flucloxacillin), oxacillin, methicillin, nafcillin, faropenem, biapenem, doripenem, ertapenem, imipenem, meropenem, panipenem, tomopenem, razupenem, cefazolin, cefacetrile, cefadroxil, cephalexin, cefaloglycin, cefalonium, cefaloridine, cephalothin, cephapirin, cefatrizine, cefazedone, cefazaflur, cefradine, cefroxadine, ceftezole, cefaclor, cefamandole, cefminox, cefonicide, ceforanide, cefotiam, cefprozil, cefbuperazone, cefuroxime, cefuzonam, cefoxitin, cefotetan, cefmetazole, loracarbef, cefixime, ceftazidime, ceftriaxone, cefcapene, cefdaloxime, cefdinir, cefditoren, cefetamet, cefmenoxime, cefodizime, cefoperazone, cefotaxime, cefpimizole, cefpiramide, cefpodoxime, cefsulodin, cefteram, ceftibuten, ceftiolene, ceftizoxime, flomoxef, latamoxef, cefepime, cefozopran, cefpirome, cefquinome, ceftobiprole, ceftaroline, CXA-101, RWJ-54428, MC-04546, ME1036, BAL30072, SYN2416, ceftiofur, cefquinome, cefovecin, aztreonam, tigemonam, carumonam, RWJ-442831, RWJ-333441, and RWJ-333442.

[Item 127]

The pharmaceutical composition according to item 125 or 126, wherein the β-lactam agent is selected from ceftazidime, biapenem, doripenem, ertapenem, imipenem, meropenem, or panipenem.

[Item 128]

The pharmaceutical composition according to item 125 or 126, wherein the β-lactam agent is selected from aztreonam, tigemonam, BAL30072, SYN2416, or carumonam.

[Item 129]

The pharmaceutical composition according to item 122, characterized in that an additional agent is concomitantly administered.

[Item 130]

The pharmaceutical composition according to item 129, wherein the additional agent is selected from an antibacterial agent, an antifungal agent, an antiviral agent, an anti-inflammatory agent, or an anti-allergic agent.

[Item 131]

The pharmaceutical composition according to item 129 or 130, wherein the additional agent is a β-lactam agent.

[Item 132]

The pharmaceutical composition according to item 130 or 131, wherein a β-lactam agent, which is the additional agent, is selected from the group consisting of amoxicillin, ampicillin (pivampicillin, hetacillin, bacampicillin, metampicillin, and talampicillin), epicillin, carbenicillin (carindacillin), ticarcillin, temocillin, azlocillin, piperacillin, mezlocillin, mecillinam (pivmecillinam), sulbenicillin, benzylpenicillin (G), clometocillin, benzathine benzylpenicillin, procaine benzylpenicillin, azidocillin, penamecillin, phenoxymethyl penicillin (V), propicillin, benzathine phenoxymethylpenicillin, phenethicillin, cloxacillin (dicloxacillin and flucloxacillin), oxacillin, methicillin, nafcillin, faropenem, biapenem, doripenem, ertapenem, imipenem, meropenem, panipenem, tomopenem, razupenem, cefazolin, cefacetrile, cefadroxil, cephalexin, cefaloglycin, cefalonium, cefaloridine, cephalothin, cephapirin, cefatrizine, cefazedone, cefazaflur, cefradine, cefroxadine, ceftezole, cefaclor, cefamandole, cefminox, cefonicide, ceforanide, cefotiam, cefprozil, cefbuperazone, cefuroxime, cefuzonam, cefoxitin, cefotetan, cefmetazole, loracarbef, cefixime, ceftazidime, ceftriaxone, cefcapene, cefdaloxime, cefdinir, cefditoren, cefetamet, cefmenoxime, cefodizime, cefoperazone, cefotaxime, cefpimizole, cefpiramide, cefpodoxime, cefsulodin, cefteram, ceftibuten, ceftiolene, ceftizoxime, flomoxef, latamoxef, cefepime, cefozopran, cefpirome, cefquinome, ceftobiprole, ceftaroline, CXA-101, RWJ-54428, MC-04546, ME1036, BAL30072, SYN2416, ceftiofur, cefquinome, cefovecin, aztreonam, tigemonam, carumonam, RWJ-442831, RWJ-333441, and RWJ-333442.

[Item 133]

The pharmaceutical composition according to item 131 or 132, wherein the β-lactam agent is selected from the group consisting of ceftazidime, biapenem, doripenem, ertapenem, imipenem, meropenem, and panipenem.

[Item 134]

The pharmaceutical composition according to item 131 or 132, wherein the β-lactam agent is selected from the group consisting of aztreonam, tigemonam, BAL30072, SYN2416, and carumonam.

[Item 135]

The compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 118 for use in treating a bacterial infection.

[Item 136]

The compound or the pharmaceutically acceptable salt thereof according to item 135, wherein the bacterial infection is a bacterial infection in which a bacteria that can have a (3-lactamase is involved.

[Item 137]

The compound or the pharmaceutically acceptable salt thereof according to item 135 or 136, wherein the bacterial infection is sepsis, febrile neutropenia, bacterial meningitis, bacterial endocarditis, otitis media, sinusitis, pneumonia, lung abscess, empyema, secondary infection of a chronic respiratory disease, pharyngolaryngitis, tonsillitis, osteomyelitis, arthritis, peritonitis, intraperitoneal abscess, cholecystitis, cholangitis, liver abscess, a deep skin infection, lymphangitis/lymphadenitis, secondary infection of trauma, burn injury, surgical wound, or the like, a urinary tract infection, a genital infection, an eye infection, or an odontogenic infection.

[Item 138]

A medicament comprised of a combination of the compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 118 and at least one agent selected from the group consisting of therapeutic agents for sepsis, febrile neutropenia, bacterial meningitis, bacterial endocarditis, otitis media, sinusitis, pneumonia, lung abscess, empyema, secondary infection of a chronic respiratory disease, pharyngolaryngitis, tonsillitis, osteomyelitis, arthritis, peritonitis, intraperitoneal abscess, cholecystitis, cholangitis, liver abscess, a deep skin infection, lymphangitis/lymphadenitis, secondary infection of trauma, burn injury, surgical wound, or the like, a urinary tract infection, a genital infection, an eye infection, and an odontogenic infection.

[Item 139]

A pharmaceutical composition comprising a β-lactam agent, wherein the pharmaceutical composition is administered with the compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 118.

[Item 140]

A method for treating a bacterial infection, characterized in that a therapeutically effective amount of the compound or the pharmaceutically acceptable salt thereof according to any one of items 1 to 118 is administered to a patient in need thereof.

[Item 141]

The method according to item 140, wherein the bacterial infection is a bacterial infection in which a bacteria that can have a β-lactamase is involved.

[Item 142]

The method according to item 140 or 141, wherein the bacterial infection is sepsis, febrile neutropenia, bacterial meningitis, bacterial endocarditis, otitis media, sinusitis, pneumonia, lung abscess, empyema, secondary infection of a chronic respiratory disease, pharyngolaryngitis, tonsillitis, osteomyelitis, arthritis, peritonitis, intraperitoneal abscess, cholecystitis, cholangitis, liver abscess, a deep skin infection, lymphangitis/lymphadenitis, secondary infection of trauma, burn injury, surgical wound, or the like, a urinary tract infection, a genital infection, an eye infection, or an odontogenic infection.

[Item 143]

The method according to any one of items 140 to 142, characterized in that an additional agent is concomitantly administered.

Specifically, the present invention is also the following.

[Item B1]

A compound represented by formula (1a) or (1b):

or a pharmaceutically acceptable salt thereof, wherein

G is an oxygen atom, a sulfur atom, or —NR^(a1)—,

X is a hydroxyl group, an optionally substituted alkoxy group, or —NR^(a2)R^(b1),

R^(a1), R^(a2), and R^(b1) are the same or different, each independently a hydrogen atom, a hydroxyl group, an optionally substituted hydrocarbyl group, or an optionally substituted heterohydrocarbyl group,

wherein R^(a2) and R^(b1) together may form an optionally substituted nitrogen-containing non-aryl heterocycle,

L¹ is a single bond, an oxygen atom, a sulfur atom, —SO—, —SO₂—, an optionally substituted hydrocarbylene group, or an optionally substituted heterohydrocarbylene group,

L² is a single bond or an optionally substituted hydrocarbylene group,

Z is a hydrogen atom, a hydroxyl group, an optionally substituted hydrocarbyl group, or an optionally substituted heterohydrocarbyl group,

one of R¹, R², and R³ is represented by formula (2):

wherein

Y is an oxygen atom, a sulfur atom, or —NR^(j)—, and R^(j) is a hydrogen atom, a hydroxyl group, or an optionally substituted hydrocarbyl group,

ring A is an optionally substituted non-aryl heterocycle,

L³ is an oxygen atom, a sulfur atom, an optionally substituted hydrocarbylene group, an optionally substituted heterohydrocarbylene group, —S(═O)—, or —S(═O)₂—,

L⁴ is a single bond, an optionally substituted hydrocarbylene group, or —C(═N—OR^(h1))—,

R^(h1) is

1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₁₀ alicyclic group, 4) C₆₋₁₀ aryl, 5) 5- or 6-membered heteroaryl, or 6) a 4- to 10-membered non-aryl heterocycle, (wherein each substituent from 2) to 6) is optionally substituted),

R⁵ is a hydrogen atom, a hydroxyl group, an optionally substituted hydrocarbyl group, or an optionally substituted heterohydrocarbyl group,

the remaining two (without the structure of formula (2) among R¹, R², and R³) are the same or different, each independently a hydrogen atom, halogen, a hydroxyl group, an optionally substituted hydrocarbyl group, or an optionally substituted heterohydrocarbyl group,

R⁴ is

1) —C(═O)R⁸,

2) —SO₂-L⁶-R⁸, (wherein R⁸ in 1) and 2) is a hydroxyl group, an optionally substituted hydrocarbyl group, or an optionally substituted heterohydrocarbyl group, and L⁶ is a single bond or an optionally substituted hydrocarbylene group), 3) —NR^(a4)R^(b3) 4) —B(OR^(m1))₂, 5) —PO(OR^(m1))(OR^(m2)), 6) optionally substituted heteroaryl, 7) an optionally substituted non-aryl heterocycle, or 8) a bioisostere of one of 1) to 7), (wherein the formulas of 1), 2), 4), 5), and 6) include a carboxylic acid isostere, and 8) may include them in duplicates),

R^(a4) and R^(b3) are the same or different, each independently having the same definition as R^(a1), R^(a2), and R^(b1), wherein a combination of R^(a4) and R^(b3), when attached to the same nitrogen atom, together may form an optionally substituted nitrogen-containing non-aryl heterocycle,

R^(m1) is a hydrogen atom or an optionally substituted hydrocarbyl group,

wherein if R^(m1) is attached to a boron atom via an oxygen atom, two R^(m1), as alkylene, together with the boron atom and two oxygen atoms, may form a non-aryl heterocycle (wherein an alkylene moiety is optionally substituted in the non-aryl heterocycle),

R^(m2) is a hydrogen atom or an optionally substituted hydrocarbyl group, and

R⁶¹, R⁶², R⁶³, and R⁶⁴ are each independently a hydrogen atom, halogen, an optionally substituted alkyl group, or -L¹-L²-Z.

[Item B2]

The compound or the pharmaceutically acceptable salt thereof according to item B1, represented by formula (1a) or (1b):

wherein

G is an oxygen atom, a sulfur atom, or —NR^(a1)—,

X is a hydroxyl group, an optionally substituted C₁₋₆ alkoxy group, or —NR^(a2)R^(b1),

R^(a1), R^(a2), and R^(b1) are the same or different, each independently

1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₁₀ alicyclic group, 4) C₆₋₁₀ aryl 5) 5- or 6-membered heteroaryl, 6) a 4- to 10-membered non-aryl heterocycle, 7) a C₁₋₆ alkylcarbonyl group, 8) a C₃₋₁₀ alicyclic carbonyl group, 9) a C₆₋₁₀ arylcarbonyl group, 10) a 5- or 6-membered heteroarylcarbonyl group, 11) a C₁₋₆ alkylsulfonyl group, 12) a C₃₋₁₀ alicyclic sulfonyl group, 13) a C₆₋₁₀ arylsulfonyl group, 14) a 5- or 6-membered heteroarylsulfonyl group, or

15) —OR^(c1),

(wherein each substituent from 2) to 14) is optionally substituted),

wherein R^(a2) and R^(b1) together may form an optionally substituted 4- to 10-membered nitrogen-containing non-aryl heterocycle,

R^(c1) is

1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₁₀ alicyclic group, 4) C₆₋₁₀ aryl, 5) 5- or 6-membered heteroaryl, or 6) a 4- to 10-membered non-aryl heterocycle, (wherein each substituent from 2) to 6) is optionally substituted),

L¹ is a single bond, an oxygen atom, a sulfur atom, —SO—, —SO₂—, —NR^(d1)—, —NR^(d1)(═O)—, or —NR^(d1)SO₂—,

L² is a single bond or an optionally substituted C₁₋₆ alkylene group,

Z is

1) a hydrogen atom, 2) a hydroxyl group, 3) a cyano group, 4) a carboxyl group, 5) a C₃₋₁₀ alicyclic group, 6) C₆₋₁₀ aryl, 7) 5- or 6-membered heteroaryl, 8) a 4- to 10-membered non-aryl heterocycle, 9) a C₁₋₆ alkoxy group, 10) a C₃₋₁₀ alicyclic oxy group, 11) a C₆₋₁₀ aryloxy group, 12) a 5- or 6-membered heteroaryloxy group, 13) a 4- to 10-membered non-aryl heterocyclyl oxy group, 14) a C₁₋₆ alkylthio group, 15) a C₃₋₁₀ alicyclic thio group, 16) a C₆₋₁₀ arylthio group, 17) a 5- or 6-membered heteroarylthio group, 18) a 4- to 10-membered non-aryl heterocyclyl thio group, (wherein each substituent from 5) to 18) is optionally substituted), 19) —SO₂—NR^(e1)R^(f1), 20) —NR^(e1)—C(═O)OR^(f1), 21) —NR^(g1)—C(═O)NR^(e1)R^(f1), 22) —NR^(e1)—C(═S)R^(f1), 23) —NR^(e1)—C(═S)OR^(f1), 24) —NR^(g1)—C(═S)NR^(e1)R^(f1), 25) —NR^(g1)—CR^(e1)(═NR^(f1)), 26) —NR^(g1)—CR^(e1)(═N—OR^(e1)), 27) —NR^(h1)—C(═NR^(g1))NR^(e1)R^(f1), 28) —NR^(h1)—C(═N—OR^(g1))NR^(e1)R^(f1), 29) —NR^(i1)—C(═NR^(h1))NR^(g1)—NR^(e1)R^(f1), 30) —NR^(i1)—C(═N—OR^(h1))NR^(g1)—NR^(e1)R^(f1), 31) —NR^(e1)—SO₂—R^(f1), 32) —NR^(g1)—SO₂—NR^(e1)R^(f1),

33) —C(═O)OR^(e1), 34) —C(═S)OR^(e1),

35) —C(═S)NR^(e1)R^(f1), 36) —C(═S)NR^(e1)OR^(f1), 37) —C(═S)NR^(g1)—NR^(e1)R^(f1), 38) —C(═NR^(e1))R^(f1), 39) —C(═N—OR^(e1))R^(f1), 40) —C(═NR^(h1))NR^(g1)—NR^(e1)R^(f1), 41) —C(═N—OR^(h1))NR^(g1)—NR^(e1)R^(f1), 42) —NR^(e1)R^(f1), 43) —NR^(g1)—NR^(e1)R^(f1), 44) —NR^(e1)OR^(f1), 45) —NR^(e1)—C(═O)R^(f1), 46) —C(═O)NR^(e1)R^(f1), 47) —C(═O)NR^(e1)OR^(f1), 48) —C(═O)NR^(g1)—NR^(e1)R^(f1),

49) —C(═O)R^(e1),

50) —C(═NR^(g1))NR^(e1)R^(f1), or 51) —C(═N—OR^(h1))NR^(e1)R^(f1),

one of R¹, R², and R³ is a group represented by formula (2):

wherein

Y is an oxygen atom, a sulfur atom, or —NR^(j)—,

ring A is an optionally substituted 4- to 20-membered non-aryl heterocycle,

L³ is

1) an oxygen atom, 2) a sulfur atom,

3) —NR^(d2)—, 4) —NR^(d2)C(═O)—,

5) —NR^(d2)SO₂—, 6) a C₁₋₆ alkylene group, 7) a C₃₋₁₀ cycloalkylene group, 8) a 4- to 10-membered non-aryl heterocyclylene group, (wherein each substituent from 6) to 8) is optionally substituted),

9) —C(═O)—, 10) —S(═O)—, or 11) —S(═O)₂—,

L⁴ is

1) a single bond, 2) a C₁₋₆ alkylene group, 3) a C₃₋₁₀ cycloalkylene group, 4) a C₆₋₁₀ arylene group, 5) a 5- or 6-membered heteroarylene group, 6) a 4- to 10-membered non-aryl heterocyclylene group, (wherein each substituent from 2) to 6) is optionally substituted), or

7) —C(═N—OR^(h1))—,

R⁵ is

1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₁₀ alicyclic group, 4) a 4- to 10-membered non-aryl heterocycle, 5) C₆₋₁₀ aryl, 6) 5- to 10-membered heteroaryl, 7) a C₁₋₆ alkylthio group, (wherein each substituent from 2) to 7) is optionally substituted, and if two substituents further substituted with the substituent of 1), 2), or 3) are each substituted on adjacent atoms within a ring, the two substituents together may further form a condensed ring structure),

8) —NR^(e1)OH,

9) a carboxyl group (—C(═O)OH), 10) a carboxylic acid isostere (wherein the carboxylic acid isostere comprises an ester group-C(═O)OR^(20a)), 11) a sulfo group (sulfonic acid group), 12) —SO₂R^(e1), 13) —SO₂—NR^(e1)R^(f1), 14) —S(═O)(═NR^(f1))R^(e1), 15) —NR^(e1)—C(═O)R^(f1), 16) —NR^(e1)—C(═O)OR^(f1), 17) —NR^(g1)—C(═O)NR^(e1)R^(f1), 18) —NR^(e1)—SO₂—R^(f1), 19) —NR^(g1)—SO₂—NR^(e1)R^(f1), 20) —N═S(═O)R^(e1)R^(f1), 21) —C(═O)NR⁵⁰R⁵¹, or 22) —NR^(e1)R^(f1) (wherein if R⁵ is the substituent of 22), -L³-L⁴-R⁵ is not —(CH₂)₁₋₄NR^(e1)R^(f1) (wherein R^(e1) and R^(f1) are a hydrogen atom, optionally substituted C₁₋₄ alkyl, an optionally substituted C₃₋₇ alicyclic group, optionally substituted 4- to 10-membered non-aryl heterocyclic group, optionally substituted C₆₋₁₀ aryl, or optionally substituted 5- to 10-membered heteroaryl)),

R^(20a) is

1) a C₁₋₆ alkyl group, 2) a C₃₋₁₀ alicyclic group, 3) C₆₋₁₀ aryl, 4) 5- or 6-membered heteroaryl, or 5) a 4- to 10-membered non-aryl heterocycle (wherein each substituent from 1) to 5) is optionally substituted),

R⁵⁰ represents

1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a hydroxyl group, 4) a C₁₋₆ alkoxy group, 5) a C₃₋₆ cycloalkoxy group, 6) a C₃₋₆ alicyclic group, 7) a 4- to 6-membered non-aryl heterocycle, 8) C₆₋₁₀ aryl, 9) 5- to 10-membered heteroaryl 10) a 4- to 6-membered non-aryl heterocyclyl oxy, 11) C₆₋₁₀ aryloxy, 12) 5- to 10-membered heteroaryloxy, 13) a C₁₋₆ alkylsulfonyl group, 14) a C₃₋₆ cycloalkoxysulfonyl group, or 15) a 4- to 6-membered non-aryl heterocyclyl sulfonyl group (wherein each substituent of 2) and 4) to 15) is optionally substituted),

R⁵¹ represents

1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₆ alicyclic group, 4) a 4- to 6-membered non-aryl heterocycle, 5) C₆₋₁₀ aryl, or 6) 5- to 10-membered heteroaryl, (wherein each substituent from 2) to 6) is optionally substituted), or

R⁵⁰ and R⁵¹ together may form an optionally substituted 4- to 7-membered nitrogen-containing non-aryl heterocycle,

the remaining two (without the structure of formula (2) among R¹, R², and R³) are the same or different, each independently a hydrogen atom, a halogen atom, an optionally substituted C₁₋₆ alkyl group, an optionally substituted C₁₋₆ alkoxy group, an optionally substituted C₁₋₆ alkylthio group, optionally substituted 5- or 6-membered heteroaryl, or —NR^(a3)R^(b2),

R^(d1), R^(d2), R^(e1), R^(f1), R^(g1), R^(h1), R^(i1), and R^(j) are the same or different, each independently

1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₁₀ alicyclic group, 4) C₆₋₁₀ aryl, 5) 5- or 6-membered heteroaryl, or 6) a 4- to 10-membered non-aryl heterocycle, (wherein each substituent from 2) to 6) is optionally substituted),

a combination of R^(e1) and R^(f1), when attached to the same nitrogen atom, together may form an optionally substituted 4- to 10-membered nitrogen-containing non-aryl heterocycle,

R⁴ is

1) —C(═O)R⁸,

2) —SO₂-L⁶-R⁸, (wherein R⁸ in 1) and 2) is —NR^(a5)R^(b4), —NR^(a5)-L⁷-B(OR^(m1))₂, —OR^(m1), or an optionally substituted C₁₋₆ alkyl group, and L⁶ is a single bond or —NR^(a6)—), 3) —NR^(a4)R^(b3) 4) —B(OR^(m1))₂, 5) —PO(OR^(m1))(OR^(m2)), 6) optionally substituted 5-membered heteroaryl, 7) an optionally substituted 5-membered non-aryl heterocycle, or 8) a bioisostere of one of 1) to 7), (wherein the formulas of 2), 4), 5), and 6) include a carboxylic acid isostere, and 8) may include them in duplicates),

R^(a3), R^(a4), R^(a5), R^(a6), R^(b2), R^(b3), and R^(b4) are the same or different, each independently having the same definition as R^(a1), R^(a2), and R^(b1), wherein a combination of R^(a3) and R^(b2), R^(a4) and R^(b3), or R^(a5) and R^(b4), when attached to the same nitrogen atom, together may form an optionally substituted 4- to 10-membered nitrogen-containing non-aryl heterocycle,

R^(m1) is

1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₁₀ alicyclic group, 4) C₆₋₁₀ aryl, 5) 5- or 6-membered heteroaryl, or 6) a 4- to 10-membered non-aryl heterocycle, (wherein each substituent from 2) to 6) is optionally substituted),

wherein if R^(m1) is attached to a boron atom via an oxygen atom, two R^(m1), as C₂₋₄ alkylene, together with the boron atom and two oxygen atoms, may form a 5- to 7-membered non-aryl heterocycle

(wherein an alkylene moiety is optionally substituted in the non-aryl heterocycle),

R^(m2) is a hydrogen atom, an optionally substituted C₁₋₆ alkyl group, or an optionally substituted C₃₋₁₀ alicyclic group,

L⁷ is an optionally substituted C₁₋₃ alkylene group,

R⁶¹, R⁶², and R⁶³ are each independently a hydrogen atom, halogen, or an optionally substituted C₁₋₆ alkyl group, and

R⁶⁴ is a hydrogen atom, halogen, an optionally substituted C₁₋₆ alkyl group, or -L¹-L²-Z.

[Item B3]

The compound or the pharmaceutically acceptable salt thereof according to item B1 or B2, wherein

L³ is

1) a C₁₋₆ alkylene group, 2) a C₃₋₁₀ cycloalkylene group, or 3) a 4- to 10-membered non-aryl heterocyclylene group, (wherein each substituent from 1) to 3) is optionally substituted), and

L⁴ is a single bond or an optionally substituted C₁₋₅ alkylene group.

[Item B4]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B3, wherein

L³ is an optionally substituted C₁₋₄ alkylene group, and

L⁴ is a single bond or an optionally substituted C₁₋₃ alkylene group.

[Item B5]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B4, wherein

L³ is —(CR³⁰R³¹)_(n1)—,

R³⁰ and R³¹, each independently, or if there are multiple instances of each of them, all of them independently represent

1) a hydrogen atom, 2) —NR^(a7)R^(a8), 3) a C₁₋₄ alkyl group, 4) C₆₋₁₀ aryl, 5) 5- to 10-membered heteroaryl, 6) a C₃₋₆ alicyclic group, 7) a 4- to 10-membered non-aryl heterocycle, (wherein each substituent from 3) to 7) is optionally substituted), or

8) —OR^(c2), or

R³⁰ and R³¹, together with the carbon atom to which they are attached, form a C₃₋₆ alicyclic group or a 4- to 6-membered non-aryl heterocycle,

R^(a7) and R^(a8) are the same or different, each independently

1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₁₀ alicyclic group, 4) C₆₋₁₀ aryl 5) 5- or 6-membered heteroaryl, 6) a 4- to 10-membered non-aryl heterocycle, 7) a C₁₋₆ alkylcarbonyl group, 8) a C₃₋₁₀ alicyclic carbonyl group, 9) a C₆₋₁₀ arylcarbonyl group, 10) a 5- or 6-membered heteroarylcarbonyl group, 11) a C₁₋₆ alkylsulfonyl group, 12) a C₃₋₁₀ alicyclic sulfonyl group, 13) a C₆₋₁₀ arylsulfonyl group, 14) a 5- or 6-membered heteroarylsulfonyl group, or

15) —OR^(c3),

(wherein each substituent from 2) to 14) is optionally substituted),

wherein R^(a7) and R^(a8) together may form an optionally substituted 4- to 10-membered nitrogen-containing non-aryl heterocycle,

R^(c2) and R^(c3) are each independently,

1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₁₀ alicyclic group, 4) C₆₋₁₀ aryl, 5) 5- or 6-membered heteroaryl, or 6) a 4- to 10-membered non-aryl heterocycle, (wherein each substituent from 2) to 6) is optionally substituted),

n1 is an integer 1, 2, 3, or 4,

L⁴ is —(CR⁴⁰R⁴¹)_(n2)—,

R⁴⁰ and R⁴¹, each independently, or if there are multiple instances of each of them, all of them independently represent

1) a hydrogen atom, 2) —NR^(a9)R^(a10), 3) a C₁₋₄ alkyl group, 4) C₆₋₁₀ aryl, 5) 5- to 10-membered heteroaryl, 6) a C₃₋₆ alicyclic group, 7) a 4- to 10-membered non-aryl heterocycle, (wherein each substituent from 3) to 7) is optionally substituted), or

8) —OR^(c4), or

R⁴⁰ and R⁴¹, together with the carbon atom to which they are attached, form a C₃₋₆ alicyclic group or a 4- to 6-membered non-aryl heterocycle,

R^(a9) and R^(a10) are the same or different, each independently

1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₁₀ alicyclic group, 4) C₆₋₁₀ aryl 5) 5- or 6-membered heteroaryl, 6) a 4- to 10-membered non-aryl heterocycle, 7) a C₁₋₆ alkylcarbonyl group, 8) a C₃₋₁₀ alicyclic carbonyl group, 9) a C₆₋₁₀ arylcarbonyl group, 10) a 5- or 6-membered heteroarylcarbonyl group, 11) a C₁₋₆ alkylsulfonyl group, 12) a C₃₋₁₀ alicyclic sulfonyl group, 13) a C₆₋₁₀ arylsulfonyl group, 14) a 5- or 6-membered heteroarylsulfonyl group, (wherein each substituent from 2) to 14) is optionally substituted), or

15) —OR^(c5),

wherein R^(a9) and R^(a10) together may form an optionally substituted 4- to 10-membered nitrogen-containing non-aryl heterocycle,

R^(c4) and R^(c5) are each independently defined the same as R^(c2) and R^(c3), and

n2 is an integer 0 (i.e., when L⁴ is a single bond), 1, 2, or 3.

[Item B6]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B5, wherein -L³-L⁴- is an optionally substituted C₁₋₂ alkylene group.

[Item B7]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B6, wherein -L³-L⁴- is a C₁₋₂ alkylene group optionally substituted with a C₁₋₃ alkyl group, an amino group, or a hydroxymethyl group, or a plurality of the same or different groups thereamong (wherein two C₁₋₃ alkyl groups, when attached to the same carbon atom, together with the carbon atom to which they are attached, may form a C₃₋₆ alicyclic group).

[Item B8]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B7, wherein

R⁵ is

1) a C₃₋₁₀ alicyclic group, 2) C₆₋₁₀ aryl, 3) 5- to 10-membered heteroaryl, 4) a C₁₋₆ alkylthio group, (wherein each substituent from 1) to 4) is optionally substituted, and if two substituents further substituted with the substituent of 2) or 3) are each substituted on adjacent atoms within a ring, the two substituents together may further form a condensed ring structure),

5) —NR^(e1)OH,

6) —C(═O)NR⁵⁰R⁵¹, 7) —SO₂—NR^(e1)R^(f1), 8) —NR^(e1)—SO₂—R^(f1),

9) —C(═O)OR²⁰, or

10) —NR^(e1)R^(f1) (wherein if R⁵ is the substituent of 10), L³ and/or L⁴ is a C₁₋₆ alkylene group that is necessarily substituted with one or more groups other than a hydrogen atom (wherein L³ or L⁴, together with said substituent, may form a C₃₋₁₀ alicyclic group or a 4- to 10-membered non-aryl heterocycle)), and

R²⁰ is

1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₁₀ alicyclic group, 4) C₆₋₁₀ aryl, 5) 5- or 6-membered heteroaryl, or 6) a 4- to 10-membered non-aryl heterocycle, (wherein each substituent from 2) to 6) is optionally substituted).

[Item B9]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B8, wherein

R⁵ is

1) C₆₋₁₀ aryl, 2) 5- to 10-membered heteroaryl, 3) —C(═O)NR⁵⁰R⁵¹,

4) —C(═O)OR²⁰, or

5) —NR^(e1)R^(f1) (wherein if R⁵ is the substituent of 5), L³ and/or L⁴ is a C₁₋₆ alkylene group that is necessarily substituted with one or more groups other than a hydrogen atom, and together with said substituent forms at least one C₃₋₁₀ alicyclic group or 4- to 10-membered non-aryl heterocycle), (wherein each substituent from 1) to 2) is optionally substituted, and any two groups thereof, when each is attached to adjacent atoms within a ring, together may further form a condensed ring structure).

[Item B10]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B9, wherein Z-L²-L¹ is an optionally substituted C₁₋₆ alkylthio group.

[Item B11]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B10, wherein R⁶¹, R⁶², R⁶³, and R⁶⁴ are each independently a hydrogen atom, a fluorine atom, or a C₁₋₃ alkyl group optionally substituted with a fluorine atom.

[Item B12]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B11, wherein R⁶¹, R⁶², R⁶³, and R⁶⁴ are each independently a hydrogen atom or a fluorine atom.

[Item B13]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B12, wherein G is an oxygen atom.

[Item B14]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B13, wherein X is a hydroxyl group or an optionally substituted C₁₋₆ alkoxy group.

[Item B15]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B14, wherein X is a hydroxyl group.

[Item B16]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B15, wherein the compounds of formulas (1a) and (1b) are represented by formulas (3a) and (3b), respectively:

wherein X, R¹, R², and R³ are defined the same as any one of items B1 to B15, and

R⁴ is selected from the group consisting of

1) —C(═O)OR^(m1) (wherein R^(m1) is a hydrogen atom, a C₁₋₆ alkyl group, a C₃₋₁₀ alicyclic group, C₆-10 aryl, 5- or 6-membered heteroaryl, or a 4- to 10-membered non-aryl heterocycle, wherein the C₁₋₆ alkyl group, the C₃₋₁₀ alicyclic group, the C₆₋₁₀ aryl, the 5- or 6-membered heteroaryl, and the 4- to 10-membered non-aryl heterocycle are each optionally substituted), and 2) a bioisostere of 1).

[Item B17]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B16, wherein R⁴ is

1) —C(═O)OH (i.e., a carboxyl group), or 2) a carboxylic acid isostere.

[Item B18]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B17, wherein the compounds of formulas (1a) and (1b) or the compounds of formulas (3a) and (3b) are represented by formulas (4a) and (4b), respectively:

wherein X, R⁴, Y, ring A, L³, L⁴, and R⁵ are defined the same as any one of items B1 to B17, and

R¹ and R² are the same or different, each independently a hydrogen atom, a halogen atom, a C₁₋₆ alkyl group, a C₁₋₆ alkoxy group, or a C₁₋₆ alkylthio group (wherein the C₁₋₆ alkyl group, the C₁₋₆ alkoxy group, and the C₁₋₆ alkylthio group are optionally substituted).

[Item B19]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B18, wherein ring A is an optionally substituted 4- to 10-membered non-aryl heterocycle.

[Item B20]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B19, wherein ring A is an optionally substituted 4- to 7-membered non-aryl heterocycle.

[Item B21]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B20, wherein Y is an oxygen atom or a sulfur atom.

[Item B22]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B21, wherein Y is an oxygen atom.

[Item B23]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B22, wherein the compounds of formulas (1a) and (1b) or the compounds of formulas (3a) and (3b) or the compounds of formulas (4a) and (4b) are represented by formulas (5a) and (5b), respectively:

wherein R¹, R², Y, L³, L⁴, and R⁵ are defined the same as any one of items B1 to B22, and ring A is an optionally substituted 4- to 6-membered nitrogen-containing non-aryl heterocycle.

[Item B24]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B2 and 10 to 23, wherein L³ is —C(═O)— or —S(═O)₂—.

[Item B25]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B2 and B10 to B24, wherein L³ is —C(═O)—.

[Item B26]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B2 and B10 to B25, wherein L⁴ is a single bond, —C(═N—OR^(h1))—, or an optionally substituted C₁₋₆ alkylene group, wherein R^(h1) is an optionally substituted C₁₋₆ alkyl group.

[Item B27]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B26, wherein R¹ and R² are the same or different, each independently selected from the group consisting of

1) a hydrogen atom, 2) a halogen atom, 3) a C₁₋₆ alkyl group, 4) a C₁₋₆ alkoxy group, and 5) a C₁₋₆ alkylthio group, (wherein each substituent from 3) to 5) is optionally substituted).

[Item B28]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B27, wherein R¹ and R² are the same or different, each independently selected from the group consisting of

1) a hydrogen atom, 2) a halogen atom, 3) a C₁₋₆ alkyl group, 4) a C₁₋₆ alkoxy group, and 5) a C₁₋₆ alkylthio group, (wherein each substituent from 3) to 5) is optionally substituted with a halogen atom).

[Item B29]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B28, wherein R¹ and R² are the same or different, each independently selected from the group consisting of

1) a hydrogen atom, 2) a halogen atom, and 3) a C₁₋₆ alkyl group optionally substituted with a halogen atom.

[Item B30]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B29, wherein R¹ and R² are the same or different, each independently selected from the group consisting of

1) a hydrogen atom, 2) a fluorine atom, and 3) a C₁₋₃ alkyl group optionally substituted with a fluorine atom.

[Item B31]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B30, wherein R¹ and R² are both hydrogen atoms.

[Item B32]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B31, wherein the compounds of formulas (1a) and (1b) or the compounds of formulas (3a) and (3b) or the compounds of formulas (4a) and (4b) or the compounds of formulas (5a) and (5b) are represented by formulas (6a) and (6b), respectively:

wherein L³, L⁴, and R⁵ are defined the same as any one of items B1 to B31,

m is an integer 1, 2, or 3,

n is an integer 1, 2, or 3, and

m+n is 2, 3, or 4.

[Item B33]

The compound or the pharmaceutically acceptable salt thereof according to item B32, wherein the compounds of formulas (6a) and (6b) are enantiomers represented by formulas (7a) and (7b):

formulas (8a) and (8b):

respectively, wherein L³, L⁴, and R⁵ are defined the same as any one of items B1 to B32, and

m and n are defined the same as item B32.

[Item B34]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B33, wherein m is 1 or 2, n is 1 or 2, and m+n is 2 or 3.

[Item B35]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B34, wherein m is 1, and n is 1.

[Item B36]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B5, B8 to B23, and B27 to B35, wherein

L³ is —(CR³⁰R³¹)_(n1)—,

R³⁰ and R³¹ each independently, or if there are multiple instances of each of them, all of them independently represent

1) a hydrogen atom, 2) an optionally substituted C₁₋₄ alkyl group, or 3) optionally substituted C₆₋₁₀ aryl,

n1 is 1, 2, or 3,

L⁴ is —(CR⁴⁰R⁴¹)_(n2)—,

R⁴⁰ and R⁴¹ each independently, or if there are multiple instances of each of them, all of them independently represent

1) a hydrogen atom, 2) —NR^(a9)R^(a10), 3) an optionally substituted C₁₋₄ alkyl group, or

4) —OR^(c4) or,

R⁴⁰ and R⁴¹, together with the carbon atom to which they are attached, form a C₃₋₆ alicyclic group or a 4- to 6-membered non-aryl heterocycle,

R^(a9), R^(a10), and R^(c4) are the same or different, each independently

1) a hydrogen atom, 2) an optionally substituted C₁₋₆ alkyl group, or 3) an optionally substituted C₃₋₁₀ alicyclic group,

wherein R^(a9) and R^(a10) together may form an optionally substituted 4- to 10-membered nitrogen-containing non-aryl heterocycle, and

n2 is 0, 1, or 2.

[Item B37]

The compound or the pharmaceutically acceptable salt thereof according to item B36, wherein n1 is 1 or 2, and n2 is 0 or 1.

[Item B38]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B5, B8 to B23, and B27 to B37, wherein

L³ is —CR³⁰R³¹—,

R³⁰ and R³¹ each independently represent

1) a hydrogen atom, 2) a C₁₋₄ alkyl group (wherein the group is optionally substituted with halogen, —NR^(a11)R^(a12), or —OR^(c6)), or 3) C₆ aryl (wherein the group is optionally substituted with halogen, —NR^(a13)R^(a14), —OR^(c7), or a C₁₋₃ alkyl group (wherein the group is optionally substituted with halogen, —NR^(a15)R^(a16), or —OR⁸)),

L⁴ is —(CR⁴⁰R⁴¹)_(n2)—,

R⁴⁰ and R⁴¹ each independently represent

1) a hydrogen atom, 2) —NR^(a9)R^(a10), 3) a C₁₋₄ alkyl group (wherein the group is optionally substituted with halogen, —NR^(a17)R^(a18), or —OR^(c9)), or

4) —OR^(c4), or

R⁴⁰ and R⁴¹, together with the carbon atom to which they are attached, form a C₃₋₆ alicyclic group,

R^(a9), R^(a10), R^(a11), R^(a12), R^(a13), R^(a14), R^(a15), R^(a16), R^(a17), R^(a18), R^(c4), R^(c6), R^(c7), R^(c8), and R^(c9) are the same or different, each independently representing

1) a hydrogen atom, or 2) a C₁₋₄ alkyl group (wherein the group is optionally substituted with halogen, —NR^(a19)R^(a20), or —OR^(c10)),

R^(a19), R^(a20), and R^(c10) are the same or different, each independently representing

1) a hydrogen atom, or 2) a C₁₋₄ alkyl group (wherein the group is optionally substituted with halogen),

wherein each combination of R^(a9) and R^(a10), R^(a11) and R^(a12), R^(a13) and R^(a14), R^(a15) and R^(a16), R^(a17) and R^(a18), or R^(a19) and R^(a20) together may form an optionally substituted 4- to 7-membered nitrogen-containing non-aryl heterocycle, and

n2 is 0 or 1.

[Item B39]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B5, B8 to B23, and B27 to B38, wherein

L³ is —CH₂—, —CH(CH₂NH₂)—, or —CH(CH₂OH)—, and

L⁴ is a single bond, —CH₂—, —CH(NH₂)—, —CMe(NH₂)—, —CEt(NH₂)—, —C(iso-Pr)(NH₂)—, —CH(CH₂NH₂)—, —CH(OH)—, —CH(CH₂OH)—, or

[Item B40]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B23 and B27 to B39, wherein R⁵ is

1) C₆₋₁₀ aryl, or 2) 5- to 10-membered heteroaryl, (wherein each substituent from 1) to 2) is optionally substituted, and if two substituents further substituted with the substituent of 1) or 2) are each substituted on adjacent atoms within a ring, the two substituents together may further form a condensed ring structure).

[Item B41]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B23 and B27 to B40, wherein

R⁵ is C₆ aryl (i.e., phenyl) or 5-membered, 6-membered, 9-membered, or 10-membered heteroaryl,

each group of R⁵ is optionally substituted with each of R^(6a) or R^(6b) at all chemically substitutable positions on a carbon atom or a nitrogen atom within a ring thereof,

wherein R^(6a), which are substituents on the carbon atom, if there are multiple instances on the same ring, are all independently selected from the group consisting of

1) a hydrogen atom, 2) a hydroxyl group, 3) a cyano group, 4) halogen, 5) a C₁₋₄ alkyl group, 6) a C₃₋₁₀ alicyclic group, 7) a C₁₋₄ alkoxy group, 8) a C₃₋₁₀ alicyclic oxy group, 9) a C₆₋₁₀ aryloxy group, 10) a 5- or 6-membered heteroaryloxy group, 11) a 4- to 10-membered non-aryl heterocyclyl oxy group, (wherein each substituent from 5) and 11) is optionally substituted), 12) —SO₂—NR^(e2)R^(f2), 13) —NR^(g2)—CR^(e2)(═NR^(f2)), 14) —NR^(g2)—CR^(e2)(═N—OR^(f2)), 15) —NR^(h2)—C(═NR^(g2))NR^(e2)R^(f2), 16) —NR^(h2)—C(═N—OR^(g2))NR^(e2)R^(f2), 17) —NR^(i2)—C(═NR^(h2))NR^(g2)—NR^(e2)R^(f2), 18) —NR^(i2)—C(═N—OR^(h2))NR^(g2)—NR^(e2)R^(f2), 19) —C(═NR^(e2))R^(f2), 20) —C(═N—OR^(e2))R^(f2), 21) —C(═NR^(h2))—NR^(e2)R^(f2), 22) —C(═NR^(h2))NR^(g2)—NR^(e2)R^(f2), 23) —C(═N—OR^(h2))NR^(g2)—NR^(e2)R^(f2), 24) —NR^(e2)R^(f2), 25) —NR^(g2)—NR^(e2)R^(f2), 26) —NR^(e2)OR^(f2), 27) —NR^(e2)—C(═O)R^(f2), 28) —C(═O)NR^(e2)R^(f2), 29) —C(═O)NR^(e2)OR^(f2), 30) —C(═O)NR^(g2)—NR^(e2)R^(f2),

31) —C(═O)R^(e2), 32) —C(═O)OR^(e2), and

33) —C(═N—OR^(h2))NR^(e2)R^(f2),

wherein R^(6b),which are substituents on the nitrogen atom, if there are multiple instances on the same ring, are all independently selected from the group consisting of

1) a hydrogen atom, 2) a hydroxyl group, 3) a C₁₋₄ alkyl group (wherein the alkyl group is optionally substituted), 4) a C₃₋₁₀ alicyclic group (wherein the alicyclic group is optionally substituted), 5) —C(═NR^(e2))R^(f2), 6) —C(═N—OR^(e2))R^(f2), 7) —SO₂—NR^(e2)R^(f2), 8) —C(═NR^(h2))—NR^(e2)R^(f2), 9) —C(═NR^(h2))NR^(g2)—NR^(e2)R^(f2), 10) —C(═N—OR^(h2))NR^(g2)—NR^(e2)R^(f2), 11) —C(═O)NR^(e2)R^(f2), 12) —C(═O)NR^(e2)OR^(f2), 13) —C(═O)NR^(g2)—NR^(e2)R^(f2),

14) —C(═O)R^(e2), and

15) —C(═N—OR^(h2))NR^(e2)R^(f2), or

if a combination of two R^(6a) or R^(6a) and R^(6b) are each substituted on adjacent atoms within a ring, the two substituents together may form an optionally substituted 5- to 6-membered heteroaryl ring or an optionally substituted 5- to 7-membered non-aryl heterocycle, which further fuses to an attachment moiety between the adjacent atoms within the ring,

R^(e2), R^(f2), R^(g2), R^(h2), and R^(i2) are the same or different, each independently

1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₁₀ alicyclic group, 4) C₆₋₁₀ aryl, 5) 5- or 6-membered heteroaryl, or 6) a 4- to 10-membered non-aryl heterocycle, (wherein each substituent from 2) to 6) is optionally substituted), and

a combination of R^(e2) and R^(f2), when attached to the same nitrogen atom, together may form an optionally substituted 4- to 10-membered nitrogen-containing non-aryl heterocycle.

[Item B42]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B23 and B27 to B41, wherein

R⁵ is C₆ aryl or 5-membered, 6-membered, 9-membered, or 10-membered heteroaryl selected from the group consisting of

d is the number of chemically substitutable positions on a ring of each group by R^(6a), and

each R^(6a) and each R^(6b) are defined the same as item B41.

[Item B43]

The compound or the pharmaceutically acceptable salt thereof according to item B41 or B42, wherein

R⁶, if there are multiple instances on the same ring, are all independently selected from the group consisting of

1) a hydrogen atom, 2) a hydroxyl group, 3) halogen, 4) a C₁₋₄ alkyl group (wherein the alkyl group is optionally substituted with NR^(e2)R^(f2), —C(═O)OR^(f2), —C(═O)NR^(e2)R^(f2), —C(═O)NR^(e2)(OR^(f2)), or a hydroxyl group), 5) a C₁₋₄ alkoxy group, 6) —NR^(e2)R^(f2), 7) —C(═O)NR^(e2)R^(f2), and

8) —C(═O)OR^(e2), and

each R^(6b), if there are multiple instances on the same ring, are all independently selected from the group consisting of

1) a hydrogen atom, 2) a hydroxyl group, and 3) a C₁₋₄ alkyl group (wherein the alkyl group is optionally substituted with NR^(e2)R^(f2), C(═O)OR^(f2), —C(═O)NR^(e2)R^(f2), —C(═O)NR^(e2)(OR^(f2)), or a hydroxyl group).

[Item B44]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B23 and B27 to B43, wherein R^(e2) and R^(f2) are the same or different, each independently a hydrogen atom, an optionally substituted C₁₋₆ alkyl group, or an optionally substituted C₃₋₁₀ alicyclic group.

[Item B45]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B23 and B27 to B44, wherein R^(e2) and R^(f2) are the same or different, each independently a hydrogen atom or an optionally substituted C₁₋₆ alkyl group.

[Item B46]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B23 and B27 to B45, wherein R^(e2) and R^(f2) are hydrogen atoms.

[Item B47]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B41 to B46, wherein R⁶ is —NR^(e2)R^(f2), and one of R^(e2) and R^(f2) is a hydrogen atom and the other is a C₁₋₄ alkyl group (wherein the alkyl group is optionally substituted with an amino group or a hydroxyl group).

[Item B48]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B23 and B27 to B39, wherein R⁵ is C(═O)NR⁵⁰R⁵¹.

[Item B49]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B23, B27 to B39, and B48, wherein

R⁵⁰ represents

1) a hydrogen atom, 2) an optionally substituted C₁₋₄ alkyl group, 3) a hydroxyl group, 4) an optionally substituted C₁₋₄ alkoxy group, or 5) an optionally substituted C₁₋₆ alkylsulfonyl group,

R⁵¹ represents

1) a hydrogen atom, or 2) an optionally substituted C₁₋₄ alkyl group, or

R⁵⁰ and R⁵¹ together may form a 4- to 6-membered nitrogen-containing non-aryl heterocycle.

[Item B50]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B23, B27 to B39, and B48 to B49, wherein

R⁵⁰ represents

1) a hydrogen atom, 2) a C₁₋₄ alkyl group (wherein the group is optionally substituted with halogen, a C₃₋₆ alicyclic group, —NR^(a21)R^(a22), or —OR^(c11)), 3) a hydroxyl group, 4) a C₁₋₄ alkoxy group (wherein the group is optionally substituted with halogen, a C₃₋₆ alicyclic group, —NR^(a23)R^(a24), or —OR^(c12)), or 5) a C₁₋₄ alkylsulfonyl group (wherein the group is optionally substituted with halogen, a C₃₋₆ alicyclic group, —NR^(a21)R^(a22), or —OR^(c11)),

R^(a21), R^(a22), R^(a23), R^(a24), R^(c11), and R^(c12) are the same or different, each independently representing

1) a hydrogen atom, or 2) a C₁₋₄ alkyl group (wherein the group is optionally substituted with halogen),

wherein each combination of R^(a21) and R^(a22) or R^(a23) and R^(a24) together may form an optionally substituted 4- to 7-membered nitrogen-containing non-aryl heterocycle, and

R⁵¹ is a hydrogen atom or C₁₋₄ alkyl (wherein the group is optionally substituted with halogen).

[Item B51]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B23, B27 to B39, and B48 to B50, wherein

R⁵⁰ represents

1) a hydrogen atom, 2) a C₁₋₄ alkyl group (wherein the group is optionally substituted with a cyclopropyl group, —NH₂, —NHMe, or a -hydroxyl group), 3) a hydroxyl group, 4) a C₁₋₄ alkoxy group (wherein the group is optionally substituted with a cyclopropyl group, —NH₂, —NHMe, or a -hydroxyl group), or 5) a C₁₋₄ alkylsulfonyl group, and

R⁵¹ is a hydrogen atom.

[Item B52]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B23 and B27 to B39, wherein R⁵ is —C(═O)OR²⁰.

[Item B53]

The compound or the pharmaceutically acceptable salt thereof according to item B52, wherein R²⁰ is

1) a hydrogen atom, or 2) an optionally substituted C₁₋₄ alkyl group.

[Item B54]

The compound or the pharmaceutically acceptable salt thereof according to item B53, wherein

L³ is —CH₂—, and

L⁴ is —CH(NH₂)— or —CMe(NH₂)—.

[Item B55]

The compound or the pharmaceutically acceptable salt thereof according to item B54, wherein L⁴ is

[Item B56]

The compound or the pharmaceutically acceptable salt thereof according to item B54 or B55, wherein L⁴ is

[Item B57]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B52 to B56, wherein R²⁰ is a hydrogen atom.

[Item B58]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B23 and B27 to B39, wherein

R⁵ is —NR^(e1)R^(f1),

L³ is —CH₂—,

L⁴ is —CR⁴⁰R⁴¹—, and

R⁴⁰ and R⁴¹, together with the carbon atom to which they are attached, form a C₃₋₆ alicyclic group.

[Item B59]

The compound or the pharmaceutically acceptable salt thereof according to item B58, wherein

R^(e1) and R^(f1) are the same or different, each independently

1) a hydrogen atom, or 2) an optionally substituted C₁₋₃ alkyl group, and

L⁴ is

[Item B60]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B2 and B10 to B35, wherein L⁴ is a single bond or a C₁₋₆ alkylene group optionally substituted with —NR²¹R²² or ═NOR²³, wherein R²¹, R²², and R²³ are each independently a hydrogen atom, an optionally substituted C₁₋₆ alkyl group, or an optionally substituted 4- to 10-membered non-aryl heterocyclyl carbonyl group.

[Item B61]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B2, B10 to B35, and B60, wherein L⁴ is a single bond, —CH₂—, —CH(NH₂)—, —CMe(NH₂)—, —CH(NHMe)-, —CD(NH₂)— (wherein D represents a heavy hydrogen atom), —CH₂CH₂—, or —CH(NH₂)—CH₂—, wherein if an amino group is present in L⁴, carbon that attaches to the amino group attaches to L³.

[Item B62]

The compound or the pharmaceutically acceptable salt thereof according to item B61, wherein

L³ is —C(═O)—, and

L⁴ is —CH(NH₂)— or —CMe(NH₂)—.

[Item B63]

The compound or the pharmaceutically acceptable salt thereof according to item B62, wherein L⁴ is an isomeric structure of one of

The compound or the pharmaceutically acceptable salt thereof according to item B62 or B63, wherein L⁴ is

[Item B65]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B2, B10 to B35, and B60 to B64, wherein R⁵ is a hydrogen atom, an optionally substituted C₁₋₆ alkyl group, an optionally substituted 4- to 10-membered non-aryl heterocycle, optionally substituted C₆₋₁₀ aryl, optionally substituted 5- or 6-membered heteroaryl, an optionally substituted C₁₋₆ alkylthio group, or —NR^(e1)OH, wherein R^(e1) is a hydrogen atom or an optionally substituted C₁₋₆ alkyl group.

[Item B66]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B2, B10 to B35, and B60 to B65, wherein R⁵ is optionally substituted 5- or 6-membered heteroaryl or optionally substituted C₆₋₁₀ aryl.

[Item B67]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B2, B10 to B35, and B60 to B66, wherein R⁵ is optionally substituted 5- or 6-membered heteroaryl.

[Item B68]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B2, B10 to B35, and B60 to B67, wherein R⁵ is an optionally substituted 4- to 10-membered non-aryl heterocycle.

[Item B69]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B2, B10 to B35, and B60 to B65, wherein L⁴ is a single bond, and R⁵ is —NR^(e1)OH, wherein R^(e1) is a hydrogen atom or an optionally substituted C₁₋₆ alkyl group.

[Item B70]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B2 and B10 to B35, wherein

L⁴ is

1) —(CH₂)_(p)—CR¹⁰(NHR¹¹)—, 2) —(CH₂)_(q)—CR¹²R¹³—, or 3) —(CH₂)_(p)—CR¹⁰(NHR¹¹)—(CH₂)_(q)—CR¹²R¹³— (wherein p and q are independently 0 or 1),

R¹⁰ is

1) a hydrogen atom, 2) a carboxyl group, or 3) —C(═O)NR^(10a)R^(10b),

R¹¹ is

1) a hydrogen atom,

2) —C(═O)R a, or

3) an optionally substituted 5- or 6-membered non-aryl heterocyclyl carbonyl group, wherein if R¹⁰ is —C(═O)NR^(10a)R^(10b), R^(10b) and R¹¹ together may form —CH₂CH₂—,

R¹² is

1) a hydrogen atom, or 2) an optionally substituted C₁₋₄ alkyl group,

R¹³ is

1) a hydrogen atom, 2) a hydroxyl group, 3) an optionally substituted C₁₋₄ alkyl group, 4) a sulfanyl group, 5) a carboxyl group, 6) an optionally substituted C₁₋₄ alkylthio group, 7) —NR^(13a)R^(13b), 8) —NR^(13a)—C(═O)R^(13b), 9) an optionally substituted 5- or 6-membered non-aryl heterocyclyl carbonylamino group, 10) —NR^(13a)—C(═O)NR^(13b)R^(13c), 11) —C(═O)NR^(13a)R^(13b), 12) —C(═O)NR^(13a)OR^(13b), 13) —S(═O)₂—R^(13a), 14) —S(═O)₂—NR^(13a)R^(13b), 15) —C(═O)NR^(13a)—S(═O)₂—R^(13b) or 16) —C(═O)NR^(13a)—S(═O)₂—NR^(13b)R^(13c), and

R^(10a), R^(10b), R^(11a), R^(13a), R^(13b), and R^(13c) are each independently a hydrogen atom or an optionally substituted C₁₋₄ alkyl group.

[Item B71]

The compound or the pharmaceutically acceptable salt thereof according to item B70, wherein R⁵ is a hydrogen atom or an optionally substituted C₁₋₄ alkyl group.

[Item B72]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B2, B10 to B35, and B60 to B67, wherein

R⁵ is selected from the group consisting of

subscript d is the number of substitutable positions on a ring of R⁵,

each R^(6a) is independently selected from the group consisting of

1) a hydrogen atom, 2) a hydroxyl group, 3) a cyano group, 4) a nitro group, 5) halogen, 6) a C₁₋₄ alkyl group, 7) a C₃₋₁₀ alicyclic group, 8) a C₁₋₄ alkoxy group, 9) a C₃₋₁₀ alicyclic oxy group, 10) a C₆₋₁₀ aryloxy group, 11) a 5- or 6-membered heteroaryloxy group, 12) a 4- to 10-membered non-aryl heterocyclyl oxy group, (wherein each substituent from 6) to 12) is optionally substituted), 13) —SO₂—NR^(e2)R^(f2), 14) —NR^(g2)—CR^(e2)(═NR^(f2)), 15) —NR^(g2)—CR^(e2)(═N—OR^(f2), 16) —NR^(h2)—C(═NR^(g2))NR^(e2)R^(f2), 17) —NR^(h2)—C(═N—OR^(g2))NR^(e2)R^(f2), 18) —NR^(i2)—C(═NR^(h2))NR^(g2)—NR^(e2)R^(f2), 19) —NR^(i2)—C(═N—OR^(h2))NR^(g2)—NR^(e2)R^(f2), 20) —C(═NR^(e2))R^(f2), 21) —C(═N—OR^(e2))R^(f2), 22) —C(═NR^(h2))—NR^(e2)R^(f2), 23) —C(═NR^(h2))NR^(g2)—NR^(e2)R^(f2), 24) —C(═N—OR^(h2))NR^(g2)—NR^(e2)R^(f2), 25) —NR^(e2)R^(f2), 26) —NR^(g2)—NR^(e2)R^(f2), 27) —NR^(e2)OR^(f2), 28) —NR^(e2)—C(═O)R^(f2), 29) —C(═O)NR^(e2)R^(f2), 30) —C(═O)NR^(e2)OR^(f2), 31) —C(═O)NR^(g2)—NR^(e2)R^(f2),

32) —C(═O)R^(e2), 33) —C(═O)OR^(e2), and

34) —C(═N—OR^(h2))NR^(e2)R^(f2), and

each R^(6b) is independently selected from the group consisting of

1) a hydrogen atom, 2) a hydroxyl group, 3) a C₁₋₄ alkyl group (wherein the alkyl group is optionally substituted), 4) a C₃₋₁₀ alicyclic group (wherein the alicyclic group is optionally substituted), 5) —C(═NR^(e2))R^(f2), 6) —C(═N—OR^(e2))R^(f2), 7) —SO₂—NR^(e2)R^(f2), 8) —C(═NR^(h2))—NR^(e2)R^(f2), 9) —C(═NR^(h2))NR^(g2)—NR^(e2)R^(f2), 10) —C(═N—OR^(h2))NR^(g2)—NR^(e2)R^(f2), 11) —C(═O)NR^(e2)R^(f2), 12) —C(═O)NR^(e2)OR^(f2), 13) —C(═O)NR^(g2)—NR^(e2)R^(f2),

14) —C(═O)R^(e2), and

15) —C(═N—OR^(h2))NR^(e2)R^(f2).

[Item B73]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B2, B10 to B35, B60 to B67, and B72, wherein

R⁵ is 5- or 6-membered aryl or heteroaryl selected from the group consisting of

subscript d is the number of substitutable positions on a ring of R⁵,

each R^(6a) is independently selected from the group consisting of

1) a hydrogen atom, 2) a hydroxyl group, 3) halogen, 4) a C₁₋₄ alkyl group (wherein the alkyl group is optionally substituted with NR^(e2)R^(f2), a 5- or 6-membered non-aryl heterocycle, —C(═O)OR^(f2), or a hydroxyl group), 5) a C₁₋₄ alkoxy group, 6) —NR^(e2)R^(f2), and

7) —C(═O)OR^(e2), and

each R^(6b) is independently selected from the group consisting of

1) a hydrogen atom, 2) a hydroxyl group, and 3) a C₁₋₄ alkyl group (wherein the alkyl group is optionally substituted with NR^(e2)R^(f2), —C(═O)NR^(e2)R^(f2), —C(═O)OR^(f2), or a hydroxyl group).

[Item B74]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B2, B10 to B35, B60 to B67, and B72 to B73, wherein

R⁵ is

[Item B75]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B2, B10 to B35, B60 to B67, and B72 to B73, wherein R^(e2) and R^(f2) are the same or different, each independently a hydrogen atom, an optionally substituted C₁₋₆ alkyl group, or an optionally substituted C₃₋₁₀ alicyclic group.

[Item B76]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B2, B10 to B35, B60 to B67, B72 to B73, and B75, wherein R^(e2) and R^(f2) are the same or different, each independently a hydrogen atom or an optionally substituted C₁₋₆ alkyl group.

[Item B77]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B2, B10 to B35, B60 to B67, B72 to B73, and B75 to B76, wherein R^(e2) and R^(f2) are hydrogen atoms.

[Item B78]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B72 to 73 and B75 to B76, wherein R^(6a) is —NR^(e2)R^(f2), and one of R^(e2) and R^(f2) is a hydrogen atom and the other is a C₁₋₄ alkyl group (wherein the alkyl group is optionally substituted with an amino group or a hydroxyl group).

[Item B79]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B2, B10 to B35, B60 to B65, and B68, wherein

R⁵ is a 4- to 6-membered non-aryl heterocycle selected from the group consisting of

subscript d is the number of substitutable positions on a ring of R⁵,

each R^(7a) is independently selected from the group consisting of

1) a hydrogen atom, 2) a hydroxyl group, 3) a cyano group, 4) halogen, 5) a C₁₋₄ alkyl group, 6) a C₃₋₁₀ alicyclic group, 7) a C₁₋₄ alkoxy group, 8) a C₃₋₁₀ alicyclic oxy group, 9) a C₆₋₁₀ aryloxy group, 10) a 5- or 6-membered heteroaryloxy group, 11) a 4- to 10-membered non-aryl heterocyclyl oxy group, (wherein each substituent from 5) and 11) is optionally substituted), 12) —SO₂—NR^(e3)R^(f3), 13) —NR^(g2)—CR^(e3)(═NR^(f3)), 14) —NR^(g2)—CR^(e3)(═N—OR^(f3)), 15) —NR^(h2)—C(═NR^(g2))NR^(e3)R^(f3), 16) —NR^(h2)—C(═N—OR^(g2))NR^(e3)R^(f3), 17) —NR^(i2)—C(═NR^(h2))NR^(g2)—NR^(e3)R^(f3), 18) —NR^(i2)—C(═N—OR^(h2))NR^(g2)—NR^(e3)R^(f3), 19) —C(═NR^(e3))R^(f3), 20) —C(═N—OR^(e3))R^(f3), 21) —C(═NR^(h2))—NR^(e3)R^(f3), 22) —C(═NR^(h2))NR^(g2)—NR^(e3)R^(f3), 23) —C(═N—OR^(h2))NR^(g2)—NR^(e3)R^(f3), 24) —NR^(e3)R^(f3), 25) —NR^(g2)—NR^(e3)R^(f3), 26) —NR^(e3)OR^(f3), 27) —NR^(e3)—C(═O)R^(f3), 28) —C(═O)NR^(e3)R^(f3), 29) —C(═O)NR^(e3)OR^(f3), 30) —C(═O)NR^(g2)—NR^(e3)R^(f3),

31) —C(═O)R^(e3), 32) —C(═O)OR^(e3), and

33) —C(═N—OR^(h2))NR^(e3)R^(f3),

each R^(7b) is independently selected from the group consisting of

1) a hydrogen atom, 2) a hydroxyl group, 3) a C₁₋₄ alkyl group (wherein the alkyl group is optionally substituted), 4) a C₃₋₁₀ alicyclic group (wherein the alicyclic group is optionally substituted), 5) —C(═NR^(e3))R^(f3), 6) —C(═N—OR^(e3))R^(f3), 7) —SO₂—NR^(e3)R^(f3), 8) —C(═NR^(h2))—NR^(e3)R^(f3), 9) —C(═NR^(h2))NR^(g2)—NR^(e3)R^(f3), 10) —C(═N—OR^(h2))NR^(g2)—NR^(e3)R^(f3), 11) —C(═O)NR^(e3)R^(f3), 12) —C(═O)NR^(e3)OR^(f3), 13) —C(═O)NR^(g2)—NR^(e3)R^(f3),

14) —C(═O)R^(e3), and

15) —C(═N—OR^(h2))NR^(e3)R^(f3), and

R^(e3) and R^(f3) are defined the same as R^(e2) and R^(f2) according to item B2.

[Item B80]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B2, B10 to B35, B60 to B65, B68, and B79, wherein

R⁵ is a 4- to 6-membered non-aryl heterocycle selected from the group consisting of

subscript d is the number of substitutable positions on a ring of R⁵,

each R^(7a) is independently selected from the group consisting of

1) a hydrogen atom, 2) a hydroxyl group, 3) halogen, 4) a C₁₋₄ alkyl group (wherein the alkyl group is optionally substituted with NR^(e3)R^(f3), a 5- or 6-membered non-aryl heterocycle, —C(═O)OR^(f3), or a hydroxyl group), 5) a C₁₋₄ alkoxy group, 6) —NR^(e3)R^(f3),

7) —C(═O)OR^(e3),

8) C₆₋₁₀ aryl, and 9) —C(═O)NR^(e3)R^(f3),

each R^(7b) is independently selected from the group consisting of

1) a hydrogen atom, 2) a hydroxyl group, and 3) a C₁₋₄ alkyl group (wherein the alkyl group is optionally substituted with NR^(e3)R^(f3), —C(═O)OR³, or a hydroxyl group), and

R^(e3) and R^(f3) are defined the same as R^(e2) and R^(f2) according to any of items B75 to B77.

[Item B81]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B2, B10 to B35, and B70 to B71, wherein

L⁴ is —CH(NH₂)—CHR¹³—, wherein carbon that attaches to the NH₂ attaches to L³,

R⁵ is a hydrogen atom, and

R¹³ is

1) —NH—C(═O)CH₃, 2) —NH—C(═O)NH₂,

3) —NH—C(═O)CH(NH₂)—CH₂C(═O)NH₂, 4) —NH—C(═O) CH₂—NH₂, 5) —NH—C(═O)CH(NH₂)—CH₂OH, or 6) a pyrrolidin-2-ylcarbonylamino group.

[Item B82]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B2, B10 to B35, and B70 to B71, wherein

L⁴ is —CH(NH₂)—CR²R³—, wherein carbon that attaches to the NH₂ attaches to L³,

R⁵ is a hydrogen atom or methyl,

R¹² is a hydrogen atom or methyl, and

R¹³ is a benzylthio group or a sulfanyl group.

[Item B83]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B2, B10 to B35, and B70 to B71, wherein

L⁴ is —CH(NH₂)—(CH₂)_(q)—CHR³—, wherein q is 0 or 1, and carbon that attaches to the NH₂ attaches to L³,

R⁵ is a hydrogen atom, and

R¹³ is

1) a carboxyl group,

2) —C(═O)NH₂, 3) —C(═O)NH(CH₃),

4) —C(═O)N(CH₃)₂, 5) —C(═O)NH—(CH₂)₂—OH, 6) —C(═O)NH—(CH₂)₂—NH₂, 7) —C(═O)NH—S(═O)₂—CH₃,

8) —C(═O)NHOH,

9) —S(═O)₂—NH₂, 10) —S(═O)₂—CH₃, or 11) a hydroxyl group.

[Item B84]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B2, B10 to B35, and B70 to B71, wherein

L⁴ is —CH(NHR¹¹)—CH₂—, wherein carbon that attaches to the NHR¹¹ attaches to L³,

R⁵ is hydrogen, and

R¹¹ is

1) —C(═O)CH(NH₂)—CH₂C(═O)NH₂, 2) —C(═O)CH₂—NH₂, 3) —C(═O)CH(CH₃)—NH₂, 4) —C(═O)CH(NH₂)—CH₂OH, or 5) pyrrolidin-2-ylcarbonyl.

[Item B85]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B2, B10 to B35, and B70 to B71, wherein

L⁴ is —CH(NHR¹¹)—CH(COOH)—, wherein carbon that attaches to the NHR¹¹ attaches to L³,

R⁵ is hydrogen, and

R¹¹ is

1) —C(═O)CH(NH₂)—CH₂C(═O)NH₂, 2) —C(═O)CH₂—NH₂, 3) —C(═O)CH(CH₃)—NH₂, 4) —C(═O)CH(NH₂)—CH₂OH, or 5) pyrrolidin-2-ylcarbonyl.

[Item B86]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B2, B10 to B35, and B70 to B71, wherein

L⁴ is —CHR¹³— or —CH₂—CHR¹³—,

R⁵ is hydrogen, and

R¹³ is —C(═O)NH₂ or —C(═O)NHOH.

[Item B87]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B2, B10 to B35, and B70 to B71, wherein

L⁴ is —CH₂—CR¹⁰(NH₂)—, wherein the CH₂ group attaches to L³,

R⁵ is hydrogen, and

R¹⁰ is a carboxy group or —C(═O)NH₂.

[Item B88]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B2, B10 to B35, and B70 to B71, wherein

L⁴ is —(CH₂)_(p)—CR¹⁰(NHR¹¹)—(CH₂)_(q)—CHR³— or —CHR³—(CH₂)_(q)—CR¹⁰(NHR¹¹)—(CH₂)_(p)—, wherein q is 0 or 1,

R⁵ is hydrogen,

(1) if L⁴ is —CHR¹³—(CH₂)_(q)—CR¹⁰(NHR¹¹)—(CH₂)_(p)—, carbon of the —CHR¹³— group attaches to L³,

p is 0,

R¹⁰ is a hydrogen atom, a carboxyl group, or —C(═O)NHR^(10b),

R¹¹ is a hydrogen atom,

R^(10b) is a hydrogen atom,

wherein if R¹⁰ is —C(═O)NHR^(10b), R^(10b) and R¹¹ together may form —CH₂CH₂—, and

R¹³ is a hydrogen atom, and

(2) if L⁴ is —(CH₂)_(p)—CR¹⁰(NHR¹¹)—(CH₂)_(q)—CHR¹³, carbon of the —(CH₂)_(p)— group attaches to L³,

p is 1,

R¹⁰ and R¹¹ are both hydrogen atoms,

R¹³ is a carboxyl group or —C(═O)NR^(13a)R^(13b), and

R^(13a) and R^(13b) are each independently a hydrogen atom or an optionally substituted C₁₋₄ alkyl group.

[Item B89]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B2, B10 to B35, and B70 to B71, wherein

L⁴ is —CR¹²(NH₂)—,

R¹² is a hydrogen atom or a methyl group, and

R⁵ is a C₁₋₄ alkyl group optionally substituted with a hydroxyl group.

[Item B90]

The compound or the pharmaceutically acceptable salt thereof according to item B1, selected from the group consisting of the compounds represented by the following names or structural formulas:

-   5-({1-[amino(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   9-[1-[2-amino-2-(1H-imidazol-4-yl)acetyl]azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   (1aS,7bR)-5-({1-[(2R)-2-amino-2-(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-9-[1-[(2R)-2-amino-2-(1H-imidazol-4-yl)acetyl]azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   (1aS,7bR)-5-({1-[(2S)-2-amino-2-(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-9-[1-[(2S)-2-amino-2-(1H-imidazol-4-yl)acetyl]azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   (1aR,7bS)-5-({1-[(2R)-2-amino-2-(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-9-[1-[(2R)-2-amino-2-(1H-imidazol-4-yl)acetyl]azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   (1aR,7bS)-5-({1-[(2S)-2-amino-2-(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-9-[1-[(2S)-2-amino-2-(1H-imidazol-4-yl)acetyl]azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   5-({1-(2-amino-2-carboxypropyl)azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   9-[1-(2-amino-2-carboxylatopropyl)azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

-   (1aS,7bR)-5-({1-[(2R)-2-amino-2-carboxypropyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-9-[1-[(2R)-2-amino-2-carboxylatopropyl]azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

-   (1aR,7bS)-5-({1-[(2R)-2-amino-2-carboxypropyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-9-[1-[(2R)-2-amino-2-carboxylatopropyl]azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

-   5-({1-[2-amino-2-(1H-imidazol-4-yl)propanoyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   9-[1-[2-amino-2-(1H-imidazol-4-yl)propanoyl]azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   (1aS,7bR)-5-({1-[(2R)-2-amino-2-(1H-imidazol-4-yl)propanoyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-9-[1-[(2R)-2-amino-2-(1H-imidazol-4-yl)propanoyl]azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   (1aS,7bR)-5-({1-[(2S)-2-amino-2-(1H-imidazol-4-yl)propanoyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2R,4S)-9-[1-[(2S)-2-amino-2-(1H-imidazol-4-yl)propanoyl]azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   (1aR,7bS)-5-({1-[(2R)-2-amino-2-(1H-imidazol-4-yl)propanoyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

-   (2S,4R)-9-[1-[(2R)-2-amino-2-(1H-imidazol-4-yl)propanoyl]azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

-   (1aR,7bS)-5-({1-[(2S)-2-amino-2-(1H-imidazol-4-yl)propanoyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic     acid

and

-   (2S,4R)-9-[1-[(2S)-2-amino-2-(1H-imidazol-4-yl)propanoyl]azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic     acid

[Item B91]

A compound represented by formula (11):

or a pharmaceutically acceptable salt thereof, wherein R^(G) is a hydroxyl group, a thiol group, or —NHR^(a1), R^(a1), X, R¹, R², R³, R⁴, R⁶¹, R⁶², R⁶³, and R⁶⁴ are defined the same as the definition according to any one of items B1 to B15, and formula (1a) is defined the same as item B1.

[Item B92]

The compound or the pharmaceutically acceptable salt thereof according to item B91, wherein the compound of formula (11) is represented by formula (12):

wherein X, R¹, R², R³, and R⁴ are defined the same as the definition according to item B16 or B17.

[Item B93]

The compound or the pharmaceutically acceptable salt thereof according to item B91 or B92, wherein the compound of formula (11) or formula (12) is represented by formula (13):

wherein X, Y, ring A, L³, L⁴, R¹, R², R⁴, and R⁵ are defined the same as the definition according to any one of items B18 to B22 and B28 to B31.

[Item B94]

The compound or the pharmaceutically acceptable salt thereof according to item B93, wherein X and R^(G) are hydroxyl groups, R⁴ is a carboxyl group, and ring A is an optionally substituted 4- to 6-membered nitrogen-containing non-aryl heterocycle.

[Item B95]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B91 to B94, wherein the compound of formula (11), formula (12), or formula (13) is represented by formula (14):

wherein X, L³, L⁴, m, n, and R⁵ are defined the same as the definition according to any one of items B32 to B59.

[Item B96]

The compound or the pharmaceutically acceptable salt thereof according to item B95, wherein the compound of formula (14) is one of the enantiomers represented by formula (15):

and formula (16):

wherein X, L³, L⁴, m, n, and R⁵ are defined the same as the definition according to any one of items B32 to B59.

[Item B97]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B91 to B96, wherein R^(G) is a hydroxyl group or a thiol group.

[Item B98]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B91 to B97, wherein R^(G) is a hydroxyl group.

[Item B99]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B91 to B98, wherein X is a hydroxyl group or a C₁₋₆ alkoxy group.

[Item B100]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B91 to B99, wherein X is a hydroxyl group.

[Item B101]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B95 to B100, wherein m is 1 or 2, n is 1 or 2, and m+n is 2 or 3.

[Item B102]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B95 to B101, wherein m is 1, and n is 1.

[Item B103]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B91 to B102, wherein L³ is defined the same as the definition according to item B24 or B25.

[Item B104]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B91 to B103, wherein L⁴ and R³ are defined the same as the definition according to any one of items B26 and B60 to B89.

[Item B105]

The compound or the pharmaceutically acceptable salt thereof according to item B92, selected from the group consisting of the compounds represented by the following names or structural formulas:

-   6-({1-[amino(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy)-3-(2-boronocyclopropyl)-2-hydroxybenzoic     acid

-   6-({1-[(2R)-2-amino-2-(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy)-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-({1-[(2S)-2-amino-2-(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy)-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-({1-[(2R)-2-amino-2-(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy)-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-({1-[(2S)-2-amino-2-(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy)-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-({1-(2-amino-2-carboxypropyl)azetidin-3-yl}oxy)-3-(2-boronocyclopropyl)-2-hydroxybenzoic     acid

-   6-({1-[(2R)-2-amino-2-carboxypropyl]azetidin-3-yl}oxy)-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-({1-[(2R)-2-amino-2-carboxypropyl]azetidin-3-yl}oxy)-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-({1-[2-amino-2-(1H-imidazol-4-yl)propanoyl]azetidin-3-yl}oxy)-3-(2-boronocyclopropyl)-2-hydroxybenzoic     acid

-   6-({1-[(2R)-2-amino-2-(1H-imidazol-4-yl)propanoyl]azetidin-3-yl}oxy)-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-({1-[(2S)-2-amino-2-(1H-imidazol-4-yl)propanoyl]azetidin-3-yl}oxy)-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

-   6-({1-[(2R)-2-amino-2-(1H-imidazol-4-yl)propanoyl]azetidin-3-yl}oxy)-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

and

-   6-({1-[(2S)-2-amino-2-(1H-imidazol-4-yl)propanoyl]azetidin-3-yl}oxy)-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic     acid

[Item B106]

A medicament comprising the compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B105.

[Item B107]

The medicament according to item B106, which is a therapeutic drug or a prophylactic drug for a bacterial infection.

[Item B108]

An agent for inhibiting β-lactamase, comprising the compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B105 as an active ingredient.

[Item B109]

A pharmaceutical composition comprising the compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B105 and a pharmaceutically acceptable carrier.

[Item B110]

The pharmaceutical composition according to item B109, further comprising an additional agent.

[Item B111]

The pharmaceutical composition according to item B110, wherein the additional agent is selected from the group consisting of an antibacterial agent, an antifungal agent, an antiviral agent, an anti-inflammatory agent, and an anti-allergic agent.

[Item B112]

The pharmaceutical composition according to item B110 or B111, wherein the additional agent is a β-lactam agent.

[Item B113]

The pharmaceutical composition according to item B111 or B112, wherein a β-lactam agent, which is the additional agent, is selected from the group consisting of amoxicillin, ampicillin (pivampicillin, hetacillin, bacampicillin, metampicillin, and talampicillin), epicillin, carbenicillin (carindacillin), ticarcillin, temocillin, azlocillin, piperacillin, mezlocillin, mecillinam (pivmecillinam), sulbenicillin, benzylpenicillin (G), clometocillin, benzathine benzylpenicillin, procaine benzylpenicillin, azidocillin, penamecillin, phenoxymethyl penicillin (V), propicillin, benzathine phenoxymethylpenicillin, phenethicillin, cloxacillin (dicloxacillin and flucloxacillin), oxacillin, methicillin, nafcillin, faropenem, biapenem, doripenem, ertapenem, imipenem, meropenem, panipenem, tomopenem, razupenem, cefazolin, cefacetrile, cefadroxil, cephalexin, cefaloglycin, cefalonium, cefaloridine, cephalothin, cephapirin, cefatrizine, cefazedone, cefazaflur, cefradine, cefroxadine, ceftezole, cefaclor, cefamandole, cefminox, cefonicide, ceforanide, cefotiam, cefprozil, cefbuperazone, cefuroxime, cefuzonam, cefoxitin, cefotetan, cefmetazole, loracarbef, cefixime, ceftazidime, ceftriaxone, cefcapene, cefdaloxime, cefdinir, cefditoren, cefetamet, cefmenoxime, cefodizime, cefoperazone, cefotaxime, cefpimizole, cefpiramide, cefpodoxime, cefsulodin, cefteram, ceftibuten, ceftiolene, ceftizoxime, flomoxef, latamoxef, cefepime, cefozopran, cefpirome, cefquinome, ceftobiprole, ceftaroline, CXA-101, RWJ-54428, MC-04546, ME1036, BAL30072, SYN2416, ceftiofur, cefquinome, cefovecin, aztreonam, tigemonam, carumonam, RWJ-442831, RWJ-333441, and RWJ-333442.

[Item B114]

The pharmaceutical composition according to item B112 or B113, wherein the β-lactam agent is selected from ceftazidime, biapenem, doripenem, ertapenem, imipenem, meropenem, or panipenem.

[Item B115]

The pharmaceutical composition according to item B112 or B113, wherein the β-lactam agent is selected from aztreonam, tigemonam, BAL30072, SYN2416, or carumonam.

[Item B116]

The pharmaceutical composition according to item B109, characterized in that an additional agent is concomitantly administered.

[Item B117]

The pharmaceutical composition according to item B116, wherein the additional agent is selected from an antibacterial agent, an antifungal agent, an antiviral agent, an anti-inflammatory agent, or an anti-allergic agent.

[Item B118]

The pharmaceutical composition according to item B116 or B117, wherein the additional agent is a β-lactam agent.

[Item B119]

The pharmaceutical composition according to item B117 or B118, wherein a β-lactam agent, which is the additional agent, is selected from the group consisting of amoxicillin, ampicillin (pivampicillin, hetacillin, bacampicillin, metampicillin, and talampicillin), epicillin, carbenicillin (carindacillin), ticarcillin, temocillin, azlocillin, piperacillin, mezlocillin, mecillinam (pivmecillinam), sulbenicillin, benzylpenicillin (G), clometocillin, benzathine benzylpenicillin, procaine benzylpenicillin, azidocillin, penamecillin, phenoxymethyl penicillin (V), propicillin, benzathine phenoxymethylpenicillin, phenethicillin, cloxacillin (dicloxacillin and flucloxacillin), oxacillin, methicillin, nafcillin, faropenem, biapenem, doripenem, ertapenem, imipenem, meropenem, panipenem, tomopenem, razupenem, cefazolin, cefacetrile, cefadroxil, cephalexin, cefaloglycin, cefalonium, cefaloridine, cephalothin, cephapirin, cefatrizine, cefazedone, cefazaflur, cefradine, cefroxadine, ceftezole, cefaclor, cefamandole, cefminox, cefonicide, ceforanide, cefotiam, cefprozil, cefbuperazone, cefuroxime, cefuzonam, cefoxitin, cefotetan, cefmetazole, loracarbef, cefixime, ceftazidime, ceftriaxone, cefcapene, cefdaloxime, cefdinir, cefditoren, cefetamet, cefmenoxime, cefodizime, cefoperazone, cefotaxime, cefpimizole, cefpiramide, cefpodoxime, cefsulodin, cefteram, ceftibuten, ceftiolene, ceftizoxime, flomoxef, latamoxef, cefepime, cefozopran, cefpirome, cefquinome, ceftobiprole, ceftaroline, CXA-101, RWJ-54428, MC-04546, ME1036, BAL30072, SYN2416, ceftiofur, cefquinome, cefovecin, aztreonam, tigemonam, carumonam, RWJ-442831, RWJ-333441, and RWJ-333442.

[Item B120]

The pharmaceutical composition according to item B118 or B119, wherein the β-lactam agent is selected from the group consisting of ceftazidime, biapenem, doripenem, ertapenem, imipenem, meropenem, and panipenem.

[Item B121]

The pharmaceutical composition according to item B118 or B119, wherein the β-lactam agent is selected from the group consisting of aztreonam, tigemonam, BAL30072, SYN2416, and carumonam.

[Item B122]

The compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B105 for use in treating a bacterial infection.

[Item B123]

The compound or the pharmaceutically acceptable salt thereof according to item B122, wherein the bacterial infection is a bacterial infection in which a bacteria that can have a (3-lactamase is involved.

[Item B124]

The compound or the pharmaceutically acceptable salt thereof according to item B122 or B123, wherein the bacterial infection is sepsis, febrile neutropenia, bacterial meningitis, bacterial endocarditis, otitis media, sinusitis, pneumonia, lung abscess, empyema, secondary infection of a chronic respiratory disease, pharyngolaryngitis, tonsillitis, osteomyelitis, arthritis, peritonitis, intraperitoneal abscess, cholecystitis, cholangitis, liver abscess, a deep skin infection, lymphangitis/lymphadenitis, secondary infection of trauma, burn injury, surgical wound, or the like, a urinary tract infection, a genital infection, eye infection, or an odontogenic infection.

[Item B125]

A medicament comprised of a combination of the compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B105 and at least one agent selected from the group consisting of therapeutic agents for sepsis, febrile neutropenia, bacterial meningitis, bacterial endocarditis, otitis media, sinusitis, pneumonia, lung abscess, empyema, secondary infection of a chronic respiratory disease, pharyngolaryngitis, tonsillitis, osteomyelitis, arthritis, peritonitis, intraperitoneal abscess, cholecystitis, cholangitis, liver abscess, a deep skin infection, lymphangitis/lymphadenitis, secondary infection of trauma, burn injury, surgical wound, or the like, a urinary tract infection, a genital infection, eye infection, and an odontogenic infection.

[Item B126]

A pharmaceutical composition comprising a β-lactam agent, wherein the pharmaceutical composition is administered with the compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B105.

[Item B127]

A method for treating a bacterial infection, characterized in that a therapeutically effective amount of the compound or the pharmaceutically acceptable salt thereof according to any one of items B1 to B105 is administered to a patient in need thereof.

[Item B128]

The method according to item B127, wherein the bacterial infection is a bacterial infection in which a bacteria that can have a β-lactamase is involved.

[Item B129]

The method according to item B127 or B128, wherein the bacterial infection is sepsis, febrile neutropenia, bacterial meningitis, bacterial endocarditis, otitis media, sinusitis, pneumonia, lung abscess, empyema, secondary infection of a chronic respiratory disease, pharyngolaryngitis, tonsillitis, osteomyelitis, arthritis, peritonitis, intraperitoneal abscess, cholecystitis, cholangitis, liver abscess, a deep skin infection, lymphangitis/lymphadenitis, secondary infection of trauma, burn injury, surgical wound, or the like, a urinary tract infection, a genital infection, an eye infection, or an odontogenic infection.

[Item B130]

The method of any one of items B127 to B129, characterized in that an additional agent is concomitantly administered.

The present invention is intended so that one or more of the features described above can be provided not only as the explicitly disclosed combinations, but also as other combinations thereof. Additional embodiments and advantages of the invention are recognized by those skilled in the art by reading and understanding the following detailed description as needed.

Advantageous Effects of Invention

The compound of the invention has excellent inhibitory action against serine-β-lactamase with a serine residue at the center of enzymatic activity. A better embodiment of the compound of the invention is expected to have a broad β-lactamase inhibitory action or metallo-β-lactamase inhibitory action with zinc (Zn²⁺) at the center of enzymatic activity against multiple types of β-lactamases. Therefore, the compound of the invention is useful alone or in concomitant use with a β-lactam agent as a therapeutic agent and/or prophylactic agent for a bacterial infection in which a bacteria that can have a β-lactamase is involved, i.e., sepsis, febrile neutropenia, bacterial meningitis, bacterial endocarditis, otitis media, sinusitis, pneumonia, lung abscess, empyema, secondary infection of a chronic respiratory disease, pharyngolaryngitis, tonsillitis, osteomyelitis, arthritis, peritonitis, intraperitoneal abscess, cholecystitis, cholangitis, liver abscess, a deep skin infection, lymphangitis/lymphadenitis, secondary infection of trauma, burn injury, surgical wound, or the like, a urinary tract infection, a genital infection, an eye infection, or an odontogenic infection.

DESCRIPTION OF EMBODIMENTS

The present invention is described hereinafter in more detail.

Throughout the entire specification, a singular expression should be understood as encompassing the concept thereof in the plural form, unless specifically noted otherwise. Thus, singular articles (e.g., “a”, “an”, “the”, and the like in the case of English) should also be understood as encompassing the concept thereof in the plural form, unless specifically noted otherwise. The terms used herein should also be understood as being used in the meaning that is commonly used in the art, unless specifically noted otherwise. Thus, unless defined otherwise, all terminologies and scientific technical terms that are used herein have the same meaning as the general understanding of those skilled in the art to which the present invention pertains. In case of a contradiction, the present specification (including the definitions) takes precedence.

The terms and the general technologies that are used herein are first described.

Unless specifically noted otherwise, the term “group” refers to a monovalent group. Examples of groups that are not a monovalent group include alkylene groups (divalent) and the like. The term “group” may also be omitted in the following descriptions of substituents or the like.

Unless specifically limited, the number of substituents when defined as “optionally substituted” or “substituted” is not particularly limited herein, as long as a substitution is possible. The number of substituents is one or multiple substituents. Moreover, unless indicated otherwise, the description for each substituent is also applicable when the substituent is a part of or a substituent of another group.

A substituent in “optionally substituted” is not particularly limited, but is preferably selected from substituent group a that consists of the following. The substituent is optionally substituted with 1 to 5 of the same or different substituents. While not particularly limited by the type of substituent, if an atom to which the substituent attaches is an oxygen atom, a nitrogen atom, or a sulfur atom, the substituent is limited to the following substituents that attaches to a carbon atom.

Substituent group α includes

1) a halogen atom 2) a hydroxyl group 3) a carboxyl group 4) a cyano group 5) a C₁₋₆ alkyl group 6) a C₂₋₆ alkenyl group 7) a C₂₋₆ alkynyl group 8) a C₁₋₆ alkoxy group 9) a C₁₋₆ alkylthio group 10) a C₁₋₆ alkylcarbonyl group 11) a C₁₋₆ alkylsulfonyl group (wherein each substituent from 5) to 11) is optionally substituted with 1 to 5 of the same or different substituents selected from substituent group β) 12) a C₃₋₁₀ alicyclic group 13) a C₃₋₁₀ alicyclic oxy group 14) a C₆₋₁₀ aryloxy group 15) a 5- or 6-membered heteroaryloxy group 16) a 4- to 10-membered non-aryl heterocyclyl oxy group 17) a C₃₋₁₀ alicyclic thio group 18) a C₆₋₁₀ arylthio group 19) a 5- or 6-membered heteroarylthio group 20) a 4- to 10-membered non-aryl heterocyclyl thio group 21) C₆₋₁₀ aryl 22) 5- or 6-membered heteroaryl 23) a 4- to 10-membered non-aryl heterocycle 24) a C₃₋₁₀ alicyclic carbonyl group 25) a C₆₋₁₀ arylcarbonyl group 26) a 5- or 6-membered heteroarylcarbonyl group 27) a 4- to 10-membered non-aryl heterocyclyl carbonyl group 28) a C₃₋₁₀ alicyclic sulfonyl group 29) a C₆₋₁₀ arylsulfonyl group 30) a 5- or 6-membered heteroarylsulfonyl group 31) a 4- to 10-membered non-aryl heterocyclyl sulfonyl group (wherein each substituent from 12) to 31) is optionally substituted with 1 to 5 of substituent group β or 1) a C₁₋₆ alkyl group) 32) —NR^(10a)R^(11a) 33) —SO₂—NR^(10b)R^(11b) 34) —NR^(10c)—C(═O)R^(11c) 35) —NR^(10d)—C(═O)OR^(11d) 36) —NR^(12a)—C(═O)NR^(10e)R^(11e) 37) —NR^(10f)—C(═S)R^(11f) 38) —NR^(10g)—C(═S)OR^(11g), 39) —NR^(12b)—C(═S)NR^(10h)R^(11h) 40) —NR^(10i)—SO₂—R^(11i) 41) —NR^(12c)—SO₂—NR^(10j)R^(11j)

42) —C(═O)OR^(10k)

43) —C(═O)NR^(10l)R^(10k) 44) —C(═O)NR^(10m)OR^(11l) 45) —C(═O)NR^(12d)—NR^(11m)

46) —C(═S)OR^(10o)

47) —C(═S)NR^(10p)R^(11n) 48) —C(═S)NR^(10q)R^(11o) 49) —C(═S)NR^(12e)—NR^(10r)R^(11p) 50) —C(═NR^(13a))R^(10s)

51) —C(═NR^(13b))CHO

52) —C(═NR^(13c))NR^(10t)R^(11q) 53) —C(═NR^(13d))NR^(12f)—NR^(10u)R^(11r) 54) —NR^(17c)—C(═NR^(13k))R^(17d) 55) —NR^(2g)—C(═NR^(13e))—NR^(10v)R^(11s) 56) —NR¹⁴—C(═NR^(13f))—NR^(12h)—NR^(10w)R^(11t)

57) —OC(═O)R^(10x) 58) —OC(═O)OR^(10y)

59) —OC(═O)NR^(10z1)R^(11u) 60) —NR^(12i)—NR^(10z2)R^(11v) 61) —NR^(10z3)OR^(11w) 62) —C(═N—OR^(13a))R^(10s)

63) —C(═N—OR^(13b))CHO

64) —C(═N—OR^(13c))NR^(10t)R^(11q) and 65) —C(═N—OR^(13d))NR^(12f)—NR^(10u)R^(11r),

substituent group β is a group consisting of

1) a halogen atom, 2) a hydroxyl group, 3) a carboxyl group, 4) a cyano group, 5) a C₃₋₁₀ alicyclic group, 6) a C₁₋₆ alkoxy group, 7) a C₃₋₁₀ alicyclic oxy group, 8) a C₁₋₆ alkylthio group, 9) a 5- or 6-membered heteroarylthio group, 10) C₆₋₁₀ aryl, 11) 5- or 6-membered heteroaryl, 12) a 4- to 10-membered non-aryl heterocycle, 13) a C₁₋₆ alkylcarbonyl group, 14) a C₃₋₁₀ alicyclic carbonyl group, 15) a C₆₋₁₀ arylcarbonyl group, 16) a 5- or 6-membered heteroarylcarbonyl group, 17) a 4- to 10-membered non-aryl heterocyclyl carbonyl group, 18) —NR^(15a)R^(16a), 19) —SO₂—NR^(15b)R^(16b), 20) —NR^(15c)—C(═O)R^(16c), 21) —NR^(17a)—C(═O)NR^(15d)R^(16d), 22) —C(═O)NR^(15e)R^(16e), 23) —C(NR^(13g))R^(15f), 24) —C(═NR^(13h))NR^(15g)R^(16f), 25) —NR^(16g)—C(═NR^(13i))R^(15h), 26) —NR^(17b)—C(═NR^(13j)) —NR^(15i)R^(16h), 27) —C(═N—OR^(13g))R^(15f), and 28) —C(═N—OR^(13h))NR^(15g)R^(16f), (wherein each substituent from 5) to 17) in substituent group P is optionally substituted with 1 to 5 substituents selected from the group consisting of a halogen atom, a hydroxyl group, a cyano group, a carboxyl group, and —NR^(18a)R^(18b)),

R^(13a), R^(13b), R^(13c), R^(13d), R^(13e), R^(13f), R^(13g), R^(13h), R^(13i), R^(13j), and R^(13k) are the same or different, each independently a hydrogen atom, a hydroxyl group, a C₁₋₆ alkyl group, or a C₁₋₆ alkoxy group,

R^(10a), R^(10b), R^(10c), R^(10d), R^(10e), R^(10f), R^(10g), R^(10h), R^(10i), R^(10j), R^(10k), R^(10l), R^(10m), R^(10n), R^(10o), R^(10p), R^(10q), R^(10r), R^(10s), R^(10t), R^(10u), R^(10v), R^(10w), R^(10x), R^(10y), R^(10z1), R^(10z2), R^(10z3), R^(11a), R^(11b), R^(11c), R^(11d), R^(11e), R^(11f), R^(11g), R^(11h), R^(11i), R^(11j), R^(11k), R^(11l), R^(11m), R^(11n), R^(11o), R^(11p), R^(11q), R^(11r), R^(11s), R^(11t), R^(11u), R^(11v), R^(11w), R^(12a), R^(12b), R^(12c), R^(12d), R^(12e), R^(12f), R^(12g), R^(12h), R^(12i), R¹⁴, R^(15a), R^(15b), R^(15c), R^(15d), R^(15e), R^(15f), R^(15g), R^(15h), R^(15i), R^(16a), R^(16b), R^(16c), R^(16d), R^(16e), R^(16f), R^(16g), R^(16h), R^(17a), R^(17b), R^(17c), and R^(17d) are the same or different, each independently a hydrogen atom or a C₁₋₆ alkyl group (wherein the group is optionally substituted with 1 to 3 of the same or different substituents selected from a hydroxyl group, a cyano group, a C₁₋₆ alkoxy group, and —NR^(18a)R^(18b)), and

R^(18a) and R^(18b) are the same or different, each independently a hydrogen atom or a C₁₋₆ alkyl group.

Preferred examples of substituents in “optionally substituted” include the following substituents.

Preferred substituent group a includes

1) a halogen atom 2) a hydroxyl group 3) a carboxyl group 4) a cyano group 5) a C₁₋₆ alkyl group 6) a C₁₋₆ alkoxy group 7) a C₁₋₆ alkylthio group 8) a C₁₋₆ alkylcarbonyl group (wherein each substituent from 5) to 8) is optionally substituted with 1 to 5 of the same or different substituents selected from substituent group β) 9) a C₃₋₁₀ alicyclic group 10) a C₃₋₁₀ alicyclic oxy group 11) a C₆₋₁₀ aryloxy group 12) a 5- or 6-membered heteroaryloxy group 13) a 4- to 10-membered non-aryl heterocyclyl oxy group 14) a C₃₋₁₀ alicyclic thio group 15) a C₆₋₁₀ arylthio group 16) a 5- or 6-membered heteroarylthio group 17) a 4- to 10-membered non-aryl heterocyclyl thio group 18) C₆₋₁₀ aryl 19) 5- or 6-membered heteroaryl 20) a 4- to 10-membered non-aryl heterocycle 21) a C₃₋₁₀ alicyclic carbonyl group 22) a C₆₋₁₀ arylcarbonyl group 23) a 5- or 6-membered heteroarylcarbonyl group 24) a 4- to 10-membered non-aryl heterocyclyl carbonyl group (wherein each substituent from 9) to 24) is optionally substituted with 1 to 5 of substituent group β or 1) a C₁₋₆ alkyl group) 25) —NR^(10a)R^(11a) 26) —SO₂—NR^(10b)R^(11b) 27) —NR^(10c)—C(═O)R^(11c) 28) —NR^(12a)—C(═O)NR^(10d)R^(11d) 29) —NR^(10e)—SO₂—R^(11e) 30) —NR^(12b)—SO₂—NR^(10f)R^(11f) 31) —C(═O)NR^(10g)R^(11g) 32) —C(═NR^(13a))R^(10h) 33) —C(═NR^(13b))NR^(10i)R^(11h) 34) —NR^(11f)—C(═NR^(13c))R^(10g) 35) —NR^(12c)—C(═NR^(13d))—NR^(10j)R^(11i) 36) —C(═N—OR^(13a))R^(10h) and 37) —C(═N—OR^(13b))NR^(10i)R^(11h),

substituent group β is preferably a group consisting of

1) a halogen atom 2) a hydroxyl group 3) a cyano group 4) a C₃₋₁₀ alicyclic group 5) a C₁₋₆ alkoxy group 6) a C₁₋₆ alkylthio group 7) a 5- or 6-membered heteroarylthio group 8) 5- or 6-membered heteroaryl 9) a 4- to 10-membered non-aryl heterocycle 10) a C₁₋₆ alkylcarbonyl group 11) a C₃₋₁₀ alicyclic carbonyl group 12) a C₆₋₁₀ arylcarbonyl group 13) a 5- or 6-membered heteroarylcarbonyl group 14) a 4- to 10-membered non-aryl heterocyclyl carbonyl group 15) —NR^(15a)R^(16a) 16) —NR^(15b)—C(═O)R^(16b) 17) —NR^(17a)—C(═O)NR^(15c)R^(16c) 18) —C(═O)NR^(15d)R^(16d) 19) —C(═NR¹³)R^(15e) 20) —C(═NR^(13f))NR^(15f)R^(16e) 21) —NR^(16f)—C(═NR^(13g))R^(15g) 22) —NR^(17b)—C(═NR^(13h))—NR^(15h)R^(16g) 23) —C(═N—OR^(13e))R^(15e) and 24) —C(═N—OR³)NR^(15f)R^(16e) (wherein each substituent from 4) to 14) in substituent group β is optionally substituted with 1 to 5 substituents selected from the group consisting of a halogen atom, a hydroxyl group, a cyano group, a carboxyl group, and —NR^(18a)R^(18b)),

R^(13a), R^(13b), R^(13c), R^(13d), R^(13e), R^(13f), R^(13g), and R^(13h) are the same or different, each independently a hydrogen atom, a hydroxyl group, a C₁₋₆ alkyl group, or a C₁₋₆ alkoxy group,

R^(10a), R^(10b), R^(10c), R^(10d), R^(10e), R^(10f), R^(10g), R^(10h), R^(10i), R^(10j), R^(11a), R^(11b), R^(11c), R^(11d), R^(11e), R^(11f), R^(11g), R^(11h), R^(11i), R^(12a), R^(12b), R^(12c), R^(15a), R^(15b), R^(15c), R^(15d), R^(15e), R^(15f), R^(15g), R^(15h), R^(16a), R^(16b), R^(16c), R^(16d), R^(16e), R^(16f), R^(16g), R^(17a), and R^(17b) are the same or different, each independently a hydrogen atom or a C₁₋₆ alkyl group (wherein the group is optionally substituted with 1 to 3 of the same or different substituents selected from a hydroxyl group, a cyano group, a C₁₋₆ alkoxy group, and —NR^(18a)R^(18b)), and

R^(18a) and R^(18b) are the same or different, each independently a hydrogen atom or a C₁₋₆ alkyl group.

More preferred examples of substituents in “optionally substituted” include the following substituents.

More preferred substituent group α includes

1) a halogen atom 2) a hydroxyl group 3) a cyano group 4) a C₁₋₆ alkyl group 5) a C₁₋₆ alkoxy group 6) a C₁₋₆ alkylthio group 7) a C₁₋₆ alkylcarbonyl group (wherein each substituent from 4) to 7) is optionally substituted with 1 to 5 of the same or different substituents selected from substituent group β) 8) a 5- or 6-membered heteroaryloxy group 9) a 4- to 10-membered non-aryl heterocyclyl oxy group 10) a 5- or 6-membered heteroarylthio group 11) a 4- to 10-membered non-aryl heterocyclyl thio group 12) C₆₋₁₀ aryl 13) 5- or 6-membered heteroaryl 14) a 4- to 10-membered non-aryl heterocycle (wherein each substituent from 4) to 14) is optionally substituted with 1 to 5 of substituent group β or 1) a C₁₋₆ alkyl group) 15) —NR^(10a)R^(11a) 16) —NR^(11b)—C(═O)R^(10b) 17) —NR^(12a)—C(═O)NR^(10c)R^(11c) 18) —C(═O)NR^(10d)R^(11d) 19) —C(═NR^(13a))R^(10e) 20) —C(═NR^(13b))NR^(10f)R^(11e) 21) —NR^(11f)—C(═NR^(13c))R^(10g) 22) —NR^(12b)—C(═NR^(13d))—NR^(10h)R^(11g) 23) —C(═N—OR^(13a))R^(10e) and 24) —C(═N—OR^(13b))NR^(10f)R^(11e),

substituent group β is more preferably

1) a halogen atom, 2) a hydroxyl group, 3) a cyano group, 4) —NR^(15a)R^(16a), 5) —NR^(15b)—C(═O)R^(16b), 6) —NR^(17a)—C(═O)NR^(15c)R^(16c), 7) —C(═O)NR^(15d)R^(16d), 8) —C(═NR^(13e))R^(15e), 9) —C(═NR^(13f))NR^(15f)R^(16e), 10) —NR^(16f)—C(═NR^(13g))R^(15g), 11) —NR^(17b)—C(═NR^(13h))—NR^(15h)R^(16g) 12) —C(═N—OR^(13e))R^(15e), and 13) —C(═N—OR^(13f))NR^(15f)R^(16e),

R^(13a), R^(13b), R^(13c), R^(13d), R^(13e), R^(13f), R^(13g), and R^(13h) are the same or different, each independently a hydrogen atom, a hydroxyl group, a C₁₋₆ alkyl group, or a C₁₋₆ alkoxy group,

R^(10a), R^(10b), R^(10c), R^(10d), R^(10e), R^(10f), R^(10g), R^(10h), R^(11a), R^(11b), R^(11c), R^(11d), R^(11e), R^(11f), R^(11g), R^(12a), R^(12b), R^(15a), R^(15b), R^(15c), R^(15d), R^(15e), R^(15f), R^(19g), R^(15h), R^(16a), R^(16b), R^(16c), R^(16d), R^(16e), R^(16f), R^(16g), R^(17a), and R^(17b) are the same or different, each independently a hydrogen atom or a C₁₋₆ alkyl group

(wherein the group is optionally substituted with 1 to 3 of the same or different substituents selected from a hydroxyl group, a cyano group, a C₁₋₆ alkoxy group, and —NR^(18a)R^(18b)), and

R^(18a) and R^(18b) are the same or different, each independently a hydrogen atom or a C₁₋₆ alkyl group.

“C₁₋₆” means that the number of carbon atoms is 1 to 6. The same applies to other numbers. For example, “C₁₋₄” means that the number of carbon atoms is 1 to 4.

A “heteroatom” refers to an oxygen atom, a nitrogen atom, a sulfur atom, or the like.

A “halogen atom” refers to a fluorine atom, chlorine atom, bromine atom, or iodine atom, preferably a fluorine atom or chlorine atom, and still more preferably a fluorine atom. A “halogen atom” is also referred to as “halogen”.

“C₁₋₆ alkyl group” refers to a linear or branched saturated hydrocarbon group with 1 to 6 carbon atoms. “C₁₋₆ alkyl group” is preferably a “C₁₋₄ alkyl group”, more preferably a “C₁₋₃ alkyl group”, and still more preferably a “C₁₋₂ alkyl group”. Specific examples of “C₁₋₆ alkyl group” include, but are not limited to, methyl, ethyl, propyl, butyl, isopropyl, isobutyl, tert-butyl, sec-butyl, isopentyl, neopentyl, tert-pentyl, 1,2-dimethylpropyl, and the like.

“C₂₋₆ alkenyl group” refers to a linear or branched unsaturated hydrocarbon group with 2 to 6 carbon atoms, comprising one or two or more carbon-carbon double bonds. “C₂₋₆ alkenyl group” is preferably a “C₂₋₄ alkenyl group”. Specific examples of “C₂₋₆ alkenyl group” include, but are not limited to, a vinyl group, 1-propylenyl group, 2-propylenyl group, 1-butenyl group, 2-butenyl group, 3-butenyl group, 2-methyl-1-propylenyl group, 2-methyl-2-propylenyl group, and the like.

“C₂₋₆ alkynyl group” refers to a linear or branched unsaturated aliphatic hydrocarbon group comprising one or two or more triple bonds. “C₂₋₆ alkynyl group” is preferably a “C₂₋₄ alkynyl group”. Specific examples thereof include, but are not limited to, an ethynyl group, 1-propynyl group, 2-propynyl group, 1-butynyl group, 1-methyl-2-propynyl group, 3-butynyl group, 1-pentynyl group, 1-hexynyl group, and the like.

“C₃₋₂₀ alicyclic group” refers to a monocyclic or bicyclic non-aromatic hydrocarbon ring with 3 to 20 carbon atoms, including those with a partially unsaturated bond, those with a partially crosslinked structure, those that have a partially spiro form, and those having one or two or more carbonyl structures. “Alicyclic group” encompasses cycloalkyl groups, cycloalkenyl groups, and cycloalkynyl groups. “C₃₋₂₀ alicyclic group” is preferably a “C₃₋₁₀ alicyclic group”, and more preferably a “C₃₋₆ alicyclic group”. Specific examples of “C₃₋₂₀ alicyclic group” include, but are not limited to, a cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclooctyl group, cyclohexadinyl group, cycloheptadinyl group, cyclooctadinyl group, adamantyl, norbornyl, and the like.

Specific examples of “C₃₋₂₀ alicyclic group” with a partially crosslinked structure include, but are not limited to, those with a structure shown below and the like.

“C₃₋₂₀ alicyclic group” also encompasses compounds fused to an aromatic ring. Specific examples thereof include the groups represented by the following and the like.

“C₃₋₁₀ alicyclic group” and “C₃₋₆ alicyclic group” refer to the “C₃₋₂₀ alicyclic group” described above wherein the “C₃₋₁₀ alicyclic group” and “C₃₋₆ alicyclic group” are a monovalent group, respectively.

“C₆₋₁₀ aryl” refers to a monocyclic or bicyclic aromatic hydrocarbon ring with 6 to 10 carbon atoms. Specific examples thereof include, as C₆ aryl, a phenyl group, and, as C₁₀ aryl, 1-naphthyl group, 2-naphthyl group, and the like. Preferred C₆₋₁₀ aryl includes C₆ aryl and C₁₀ aryl.

“Heteroaryl” refers to an aromatic heterocycle comprising one or more of the same or different heteroatoms selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom. Heretoaryl is preferably the “5- or 6-membered heteroaryl”, “5- to 10-membered heteroaryl”, or “9- or 10-membered heteroaryl” described below.

“5- or 6-membered heteroaryl” refers to a monocyclic aromatic heterocycle consisting of 5 to 6 atoms, comprising 1 to 4 of the same or different heteroatoms selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom. “5- or 6-membered heteroaryl” is also referred to as a “5- to 6-membered heteroaryl ring”.

“5- to 10-membered heteroaryl” refers to a monocyclic or bicyclic aromatic heterocycle consisting of 5 to 10 atoms, comprising 1 to 4 of the same or different heteroatoms selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom.

“9- or 10-membered heteroaryl” refers to a bicyclic aromatic heterocycle consisting of 9 to 10 atoms, comprising 1 to 4 of the same or different heteroatoms selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom.

“5- or 6-membered nitrogen-containing heteroaryl” refers to a monocyclic aromatic heterocycle consisting of 5 to 6 atoms, comprising 0 to 3 of the same or different heteroatoms selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom, in addition to 1 nitrogen atom. “5- or 6-membered nitrogen-containing heteroaryl” is also referred to as a “5- to 6-membered nitrogen-containing heteroaryl ring”.

Specific examples of “6-membered heteroaryl” include, but are not limited to, pyridine, pyridazine, pyrimidine, pyrazine, and the like.

Specific examples of “5-membered heteroaryl” include, but are not limited to, thiophene, pyrrole, thiazole, isothiazole, pyrazole, imidazole, furan, oxazole, isoxazole, oxadiazole, thiadiazole, triazole, tetrazole, and the like. 5-membered heteroaryl is preferably triazole or imidazole, and more preferably imidazole.

Specific examples of “5- or 6-membered heteroaryl” include the specific examples for “5-membered heteroaryl” and “6-membered heteroaryl” described above.

Specific examples of “9-membered heteroaryl” include, but are not limited to, indole, isoindole, indazole, benzimidazole, imidazopyridine, benzothiazole, azaindole, purine, and the like.

Specific examples of “10-membered heteroaryl” include, but are not limited to, quinoline, isoquinoline, quinazoline, phthalazine, and the like.

Specific examples of “9- or 10-membered heteroaryl” include the specific examples for the “9-membered heteroaryl” and “10-membered heteroaryl” described above.

“Optionally substituted heteroaryl” can be substituted with a substituent in “optionally substituted” described above. For example, pyridine, when substituted with a hydroxyl group at position 2, has the following tautomers 2-hydroxypyridine and 2-pyridone.

Thus, 2-pyridone is also encompassed by “optionally substituted heteroaryl” herein. Heteroaryl may form a condensed ring with an alicyclic group, aryl or a non-aryl heterocycle.

“Non-aryl heterocycle” refers to a monocyclic or bicyclic nonaromatic heterocycle comprising one or two or more of the same or different heteroatoms selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom, including those with a partially unsaturated bond, those with a partially crosslinked structure, and those that have a partially spiro form. A non-aryl heterocycle may form a condensed ring with aryl or heteroaryl and is preferably the following “4- to 20-membered non-aryl heterocycle”.

“4- to 20-membered non-aryl heterocycle” refers to a monocyclic or bicyclic non-aromatic heterocycle comprised of 4 to 20 atoms, comprising one or two or more of the same or different heteroatoms selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom, including those with a partially unsaturated bond, those with a partially crosslinked structure, and those that have a partially spiro form. A non-aryl heterocycle may form a condensed ring with aryl or heteroaryl. When fused to, for example, C₆₋₁₀ aryl or 5- or 6-membered heteroaryl, such a heterocycle is still encompassed by a non-aryl heterocycle. Such a heterocycle may comprise one or two or more carbonyl, thiocarbonyl, sulfinyl, or sulfonyl to make up the non-aryl heterocycle. For example, lactam, thiolactam, lactone, thiolactone, cyclic imide, cyclic carbamate, cyclic thiocarbamate, and other cyclic groups are also encompassed by said non-aryl heterocycle. In this regard, oxygen atoms of carbonyl, sulfinyl, and sulfonyl and sulfur atoms of thiocarbonyl are not included in the number of 4 to 20 members (size of ring) or the number of heteroatoms constituting the ring. Specific examples of “4- to 20-membered non-aryl heterocycle” include, but are not limited to, azetidine, pyrrolidine, piperidine, piperazine, morpholine, homopiperidine, oxetane, tetrahydrofuran, tetrahydropyran, and the like, those with a structure shown below, and the like.

Specific examples of “4- to 20-membered non-aryl heterocycle” with partial crosslinking or spiro structure include, but are not limited to, those with a structure shown below and the like.

“Nitrogen-containing non-aryl heterocycle” refers to a monocyclic or bicyclic nonaromatic heterocycle comprising 0 or 1 or more of the same or different heteroatoms selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom, in addition to one nitrogen atom, including those with a partially unsaturated bond, those with a partially crosslinked structure, and those that have a partially spiro form and is preferably the following “4- to 20-membered nitrogen-containing non-aryl heterocycle”.

“4- to 20-membered nitrogen-containing non-aryl heterocycle” refers to a monocyclic or bicyclic non-aromatic heterocycle comprised of 4 to 20 atoms, comprising 0 or 1 of the same or different heteroatoms selected from the group consisting of an oxygen atom, a nitrogen atom, and a sulfur atom, in addition to 1 nitrogen atom, including those with a partially unsaturated bond, those with a partially crosslinked structure, and those that have a partially spiro form.

“4- to 10-membered non-aryl heterocycle” refers to the “4- to 20-membered non-aryl heterocycle” described above wherein “4- to 10-membered non-aryl heterocycle” is a substituent that is a monovalent group.

“4- to 10-membered nitrogen-containing non-aryl heterocycle”, “4- to 7-membered nitrogen-containing non-aryl heterocycle”, “5- to 7-membered nitrogen-containing non-aryl heterocycle”, and “4- to 6-membered nitrogen-containing non-aryl heterocycle” refer to the “4- to 20-membered nitrogen-containing non-aryl heterocycle” described above wherein the “4- to 10-membered nitrogen-containing non-aryl heterocycle”, “4- to 7-membered nitrogen-containing non-aryl heterocycle”, “5- to 7-membered nitrogen-containing non-aryl heterocycle”, and “4- to 6-membered nitrogen-containing non-aryl heterocycle” are substituents that are a monovalent group, respectively.

“5- to 7-membered non-aryl heterocycle” refers to the “4- to 20-membered non-aryl heterocycle” described above wherein “5- to 7-membered non-aryl heterocycle” is a substituent that is a monovalent group.

“4- to 7-membered non-aryl heterocycle” and “4- to 6-membered non-aryl heterocycle” refer to the “4- to 20-membered non-aryl heterocycle” described above wherein “4- to 7-membered non-aryl heterocycle” and “4- to 6-membered non-aryl heterocycle” are substituents that are a monovalent group, respectively.

Specific examples of “4-membered non-aryl heterocycle” include, but are not limited to, azetidine, oxetane, thietane, and the like.

Specific examples of “4-membered non-aryl heterocycle” with a partially unsaturated bond include, but are not limited to, those with a structure shown below and the like.

Specific examples of “5-membered non-aryl heterocycle” include, but are not limited to, pyrrolidine, pyrrolidone, oxazolidinone, tetrahydrofuran, tetrahydrothiophene, and the like.

Specific examples of “5-membered non-aryl heterocycle” with a partially unsaturated bond include, but are not limited to, those with a structure shown below and the like.

Specific examples of “5-membered non-aryl heterocycle” with a partially crosslinked structure include, but are not limited to, those with a structure shown below and the like.

Specific examples of “5-membered non-aryl heterocycle” comprising carbonyl, thiocarbonyl, or the like include, but are not limited to, those with a structure shown below and the like.

Specific examples of “6-membered non-aryl heterocycle” include, but are not limited to, piperidine, piperazine, morpholine, tetrahydropyran, tetrahydrothiopyran, and the like.

Specific examples of “6-membered non-aryl heterocycle” with a partially unsaturated bond include, but are not limited to, those with a structure shown below and the like.

Specific examples of “6-membered non-aryl heterocycle” with a partially crosslinked structure include, but are not limited to, those with a structure shown below and the like.

“C₁₋₆ alkoxy group” refers to a “C₁₋₆ alkyloxy group”, and the C₁₋₆ alkyl moiety is defined the same as the C₁₋₆ alkyl group described above. “C₁₋₆ alkoxy group” is preferably a “C₁₋₄ alkoxy group”, more preferably a “C₁₋₃ alkoxy group”, and still more preferably a “C₁₋₂ alkoxy group”. Specific examples of “C₁₋₆ alkoxy group” include, but are not limited to, a methoxy group, ethoxy group, propoxy group, butoxy group, isopropoxy group, isobutoxy group, tert-butoxy group, sec-butoxy group, isopentyloxy group, neopentyloxy group, tert-pentyloxy group, 1,2-dimethylpropoxy group, and the like.

“C₃₋₁₀ alicyclic oxy group” refers to a (C₃₋₁₀ alicyclic group)-O— group, and the C₃₋₁₀ alicyclic moiety is defined the same as a C₃₋₁₀ alicyclic group. “C₃₋₆ alicyclic oxy group” refers to a (C₃₋₆ alicyclic group)-O— group, and the C₃₋₆ alicyclic moiety is defined the same as a C₃₋₆ alicyclic group. “C₃₋₆ alicyclic oxy group” is preferably a “C₃₋₅ alicyclic oxy group”. Specific examples of “C₃₋₆ alicyclic oxy group” include, but are not limited to, a cyclopropyloxy group, cyclobutyloxy group, cyclopentyloxy group, cyclohexyloxy group, and the like.

The C₆₋₁₀ aryl moiety of a “C₆₋₁₀ aryloxy group” is defined the same as the C₆₋₁₀ aryl described above. “C₆₋₁₀ aryloxy group” is preferably a “C₆ or C₁₀ aryloxy group”. Specific examples of “C₆₋₁₀ aryloxy group” include, but are not limited to, a phenoxy group, 1-naphthyloxy group, 2-naphthyloxy group, and the like.

The 5- or 6-membered heteroaryl moiety of “5- or 6-membered heteroaryloxy group” is defined the same as the “5-membered heteroaryl” or “6-membered heteroaryl” described above. Specific examples of “5- or 6-membered heteroaryloxy group” include, but are not limited to, a pyrazoyloxy group, triazoyloxy group, thiazoyloxy group, thiadiazoyloxy group, pyridyloxy group, pyridazoyloxy group, and the like.

The 4- to 10-membered non-aryl heterocycle moiety of “4- to 10-membered non-aryl heterocyclyl oxy group” is defined the same as the “4- to 10-membered non-aryl heterocycle” described above. “4- to 10-membered non-aryl heterocyclyl oxy group” is preferably a “4- to 6-membered non-aryl heterocyclyl oxy group”. Specific examples of “4- to 10-membered non-aryl heterocyclyl oxy group” include, but are not limited to, a tetrahydrofuranyloxy group, tetrahydropyranyloxy group, azetidinyloxy group, pyrrolidinyloxy group, piperidinyloxy group, and the like.

The C₁₋₆ alkyl moiety of “C₁₋₆ alkylthio group” is defined the same as the C₁₋₆ alkyl described above. “C₁₋₆ alkylthio group” is preferably a “C₁₋₄ alkylthio group”, and more preferably a “C₁₋₃ alkylthio group”. Specific examples of “C₁₋₆ alkylthio group” include, but are not limited to, a methylthio group, ethylthio group, propylthio group, butylthio group, isopropylthio group, isobutylthio group, tert-butylthio group, sec-butylthio group, isopentylthio group, neopentylthio group, tert-pentylthio group, 1,2-dimethylpropylthio group, and the like.

“C₃₋₁₀ alicyclic thio group” refers to a (C₃₋₁₀ alicyclic group)-S— group, and the C₃₋₁₀ alicyclic moiety is defined the same as the C₃₋₁₀ alicyclic group described above. “C₃₋₁₀ alicyclic thio group” is preferably a “C₃₋₆ alicyclic thio group”. Specific examples of “C₃₋₆ alicyclic thio group” include, but are not limited to, a cyclopropylthio group, cyclobutylthio group, cyclopentylthio group, cyclohexylthio group, and the like.

The C₆₋₁₀ aryl moiety of “C₆₋₁₀ arylthio group” is defined the same as the C₆₋₁₀ aryl described above. “C₆₋₁₀ arylthio group” is preferably a “C₆ or C₁₀ arylthio group”. Specific examples of “C₆₋₁₀ arylthio group” include, but are not limited to, a phenylthio group, 1-naphthylthio group, 2-naphthylthio group, and the like.

The 5- or 6-membered heteroaryl moiety of “5- or 6-membered heteroarylthio group” is defined the same as the “5-membered heteroaryl” or “6-membered heteroaryl” described above. Specific examples of “5- or 6-membered heteroarylthio group” include, but are not limited to, a pyrazoylthio group, triazoylthio group, thiazoylthio group, thiadiazoylthio group, pyridylthio group, pyridazoylthio group, and the like.

The 4- to 10-membered non-aryl heterocycle moiety of “4- to 10-membered non-aryl heterocyclyl thio group” is defined the same as the “4- to 10-membered non-aryl heterocycle” described above. “4- to 10-membered non-aryl heterocyclyl thio group” is preferably a “4- to 6-membered non-aryl heterocyclyl thio group”. Specific examples of “4- to 10-membered non-aryl heterocyclyl thio group” include, but are not limited to, a tetrahydropyranylthio group, piperidinylthio group, and the like.

“C₁₋₆ alkylcarbonyl group” refers to a carbonyl group substituted with the “C₁₋₆ alkyl group” described above. “C₁₋₆ alkylcarbonyl group” is preferably a “C₁₋₄ alkylcarbonyl group”. Specific examples of “C₁₋₆ alkylcarbonyl group” include, but are not limited to, an acetyl group, propionyl group, butyryl group, and the like.

“C₃₋₁₀ alicyclic carbonyl group” refers to a carbonyl group substituted with the “C₃₋₁₀ alicyclic group” described above. “C₃₋₁₀ alicyclic carbonyl group” is preferably a “C₃₋₆ alicyclic carbonyl group”. Specific examples of “C₃₋₁₀ alicyclic carbonyl group” include, but are not limited to, a cyclopropylcarbonyl group, cyclopentylcarbonyl group, and the like.

“C₆₋₁₀ arylcarbonyl group” refers to a carbonyl group substituted with the “C₆₋₁₀ aryl” described above. “C₆₋₁₀ arylcarbonyl group” is preferably a “C₆ or C₁₀ arylcarbonyl group”. Specific examples of “C₆₋₁₀ arylcarbonyl group” include, but are not limited to, a benzoyl group, 1-naphthylcarbonyl group, 2-naphthylcarbonyl group, and the like.

“5- or 6-membered heteroarylcarbonyl group” refers to a carbonyl group substituted with the “5- or 6-membered heteroaryl” described above. Specific examples of “5- or 6-membered heteroarylcarbonyl group” include, but are not limited to, a pyrazoylcarbonyl group, triazoylcarbonyl group, thiazoylcarbonyl group, thiadiazoylcarbonyl group, pyridylcarbonyl group, pyridazoylcarbonyl group, and the like.

“4- to 10-membered non-aryl heterocyclyl carbonyl group” refers to a carbonyl group substituted with the “4- to 10-membered non-aryl heterocycle” described above. “4- to 10-membered non-aryl heterocyclyl carbonyl group” is preferably a “4- to 6-membered non-aryl heterocyclyl carbonyl group”. Specific examples of “4- to 10-membered non-aryl heterocyclyl carbonyl group” include, but are not limited to, an azetidinylcarbonyl group, pyrrolidinylcarbonyl group, piperidinylcarbonyl group, morpholinylcarbonyl group, and the like.

“C₁₋₆ alkylsulfonyl group” refers to a sulfonyl group substituted with the “C₁₋₆ alkyl group” described above. “C₁₋₆ alkylsulfonyl group” is preferably a “C₁₋₄ alkylsulfonyl group”. Specific examples of “C₁₋₆ alkylsulfonyl group” include, but are not limited to, a methylsulfonyl group, propylsulfonyl group, butylsulfonyl group, and the like.

“C₃₋₁₀ alicyclic sulfonyl group” refers to a sulfonyl group substituted with the “C₃₋₁₀ alicyclic group” described above. “C₃₋₁₀ alicyclic sulfonyl group” is preferably a “C₃₋₆ alicyclic sulfonyl group”. Specific examples of “C₃₋₁₀ alicyclic sulfonyl group” include, but are not limited to, a cyclopropylsulfonyl group, cyclobutylsulfonyl group, cyclopentylsulfonyl group, cyclohexylsulfonyl group, and the like.

“C₆₋₁₀ arylsulfonyl group” refers to a sulfonyl group substituted with the “C₆₋₁₀ aryl” described above. “C₆₋₁₀ arylsulfonyl group” is preferably a “C₆ or C₁₀ arylsulfonyl group”. Specific examples of “C₆₋₁₀ arylsulfonyl group” include, but are not limited to, a phenylsulfonyl group, 1-naphthylsulfonyl group, 2-naphthylsulfonyl group, and the like.

“5- or 6-membered heteroarylsulfonyl group” refers to a sulfonyl group substituted with the “5- or 6-membered heteroaryl” described above. Specific examples of “5- or 6-membered heteroarylsulfonyl group” include a pyrazoylsulfonyl group, triazoylsulfonyl group, thiazoylsulfonyl group, thiadiazoylsulfonyl group, pyridylsulfonyl group, pyridazoylsulfonyl group, and the like.

“C₁₋₆ alkylene group” refers to a substituent that is a divalent group due to removing two hydrogen atoms from saturated hydrocarbon with 1 to 6 carbon atoms. “C₁₋₃ alkylene group” and “C₂₋₄ alkylene group” refer to substituents that are divalent groups due to removing two hydrogen atoms from saturated hydrocarbon with 1 to 3 carbon atoms and 2 to 4 carbon atoms, respectively.

“C₃₋₁₀ cycloalkylene group” refers to a substituent that is a divalent group due to removing two hydrogen atoms from saturated cyclic hydrocarbon with 3 to 10 carbon atoms. “C₃₋₆ cycloalkylene group” and “C₄₋₆ cycloalkylene group” refer to substituents that are divalent groups due to removing two hydrogen atoms from saturated cyclic hydrocarbon with 3 to 6 carbon atoms and 4 to 6 carbon atoms, respectively.

“C₆₋₁₀ arylene group” refers to a substituent that is a divalent group due to removing two hydrogen atoms from aromatic hydrocarbon with 6 to 10 carbon atoms. “C₆ arylene group” refers to a substituent that is a divalent group due to removing two hydrogen atoms from aromatic hydrocarbon with 6 carbon atoms.

“5- or 6-membered heteroarylene group” refers to a substituent that is a divalent group due to removing two hydrogen atoms from a 5- or 6-membered heteroaryl ring. “5-membered heteroarylene group” and “6-membered heteroarylene group” refer to substituents that are divalent groups due to removing two hydrogen atoms from 5-membered and 6-membered heteroaryl rings, respectively.

“4- to 10-membered non-aryl heterocyclylene group” refers to a substituent that is a divalent group due to removing two hydrogen atoms from a 4- to 10-membered non-aryl heterocycle. “4- to 5-membered non-aryl heterocyclylene group” and “4- to 6-membered non-aryl heterocyclylene group” refer to substituents that are divalent groups due to removing two hydrogen atoms from 4- to 5-membered and 4- to 6-membered non-aryl heterocycles, respectively.

“Hydrocarbyl group”, as used herein, refers to a monovalent group produced by removing a hydrogen atom from hydrocarbon consisting of only a carbon atom and hydrogen atoms. Hydrocarbyl can be aliphatic (linear or branched), alicyclic group, or aromatic (aryl). Examples thereof include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, a cyclopentyl group, a cyclohexyl group, a phenyl group, and the like. “Optionally substituted hydrocarbyl group” refers to a hydrocarbyl group that is substituted with a substituent described above. “Optionally substituted hydrocarbyl group” is optionally substituted with an oxo group (═O group), a thioxo group (═S group), or an imino group (═NR). Examples thereof include a formyl group, an acetyl group, and the like.

“Hydrocarbylene group”, as used herein, refers to a divalent group produced by removing two hydrogen atoms from hydrocarbon consisting of only a carbon atom and hydrogen atoms. Hydrocarbylene can be aliphatic (linear or branched), alicyclic group, or aromatic (aryl). Examples thereof include a methylene group, an ethylene group, an n-propylene group, an isopropylene group, a cyclopentandiyl group, a cyclohexandiyl group, a phenylene group, and the like. “Optionally substituted hydrocarbylene group” refers to a hydrocarbylene group that is substituted with a substituent described above. “Optionally substituted hydrocarbylene group” is optionally substituted with an oxo group (═O group), a thioxo group (═S group), or an imino group (═NR).

“Heterohydrocarbyl group”, as used herein, refers to a group wherein at least one carbon atom (may be all carbon atoms) of a hydrocarbyl group is substituted with a heteroatom. Examples of heteroatom include O, N, S, and P. Examples of heterohydrocarbyl group include heteroaryl, non-aryl heterocycle, alkoxy group, alkylthio group, carboxy group, carboxylic acid isostere (wherein the carboxylic acid isostere comprises an ester group-C(═O)OR^(20a)), —NR^(e1)—C(═O)R^(f1), —NR^(e1)—C(═O)OR^(f1), —NR^(g1)—C(═O)NR^(e1)R^(f1)—C(═O)NR⁵⁰R⁵¹—C(═O)NR⁵⁰R⁵¹ (wherein R^(20a), R^(e1), R^(f1), R^(g1), R⁵⁰, and R⁵¹ are defined the same as item 1 or 2 herein), and the like. Examples thereof include a methoxy group, an ethoxy group, a cyano group, an imidazole group, a pyridinyl group, a pyrazole group, a triazole group, a pyrazinyl group, a pyridazinyl group, a pyrimidinyl group, and the like. “Optionally substituted heterohydrocarbyl group” refers to a heterohydrocarbyl group that is substituted with a substituent described above. “Optionally substituted heterohydrocarbyl group” is optionally substituted with an oxo group (═O group), a thioxo group (═S group), or an imino group (═NR). Examples thereof include a carboxyl group, a methoxycarbonyl group, an aminocarbonyl group, a hydroxyaminocarbonyl group, and the like.

“Heterohydrocarbylene group”, as used herein, refers to a group wherein at least one carbon atom (may be all carbon atoms) of a hydrocarbylene group is substituted with a heteroatom. Examples of heteroatom include O, N, S. and P. Examples of heterohydrocarbylene group include heteroarylene, a non-aryl heterocyclyl diyl group, an alkyleneoxy group, an alkylenethio group, and the like. Examples thereof include a methyleneoxy group, an ethyleneoxy group, an imino group (—NR— group), an imidazole diyl group, a pyridine diyl group, a pyrazole diyl group, a triazole diyl group, a pyradine diyl group, a pyridazine diyl group, a pyrimidine diyl group, and the like. “Optionally substituted heterohydrocarbylene group” refers to a heterohydrocarbylene group substituted with a substitutent described above. “Optionally substituted heterohydrocarbylene group” is optionally substituted with an oxo group (═O group), a thioxo group (═S group), or an imino group (═NR). Examples thereof include a carbonyloxy group, a methyleneoxycarbonyl group, an aminocarbonyl group, a hydroxyaminocarbonyl group, an iminocarbonyl group (—NRC(═O)— group), an iminosulfonyl group (—NRSO₂- group), optionally substituted —NH—, optionally substituted —NH—SO₂—, and the like.

A bond intersecting a wavy line in the description of a specific structure of R⁵ indicates a bond with L⁴. A bond intersecting a bond between ring atoms means that there are variables (e.g., R^(6a), R^(7a), and the like) at each of the substitutable positions on a monocycle or fused polycycle including the ring atoms. For example, for a monocyclic 5-membered ring (heteroaryl),

(wherein d is 3) is one of

and L⁴ attaches to a ring carbon atom of the 5-membered ring. For example, for a monocyclic 6-membered ring (heteroaryl),

(wherein d is 4) is one of

and L⁴ attaches to a ring carbon atom of the 6-membered ring. Alternatively, for example, for a monocyclic 5-membered ring (non-aryl heterocycle),

(wherein d is 7) is one of

and L⁴ attaches to a ring carbon atom of the 5-membered ring. For example, for a monocyclic 6-membered ring (non-aryl heterocycle),

(wherein d is 10) is one of

and L⁴ attaches to a ring carbon atom of the 6-membered ring.

Subscript d is the number of substitutable positions on a ring of R⁵, but is a number of substitutable positions excluding the attachment position to L⁴.

“Bioisostere” refers to another partial structure (functional group) serving the same biological role as a group (e.g., carboxyl group) in a drug molecule (prodrug structures are also encompassed as a concept of a bioisostere in the present invention). “Carboxylic acid isostere” refers to a bioisostere of carboxylic acid. Examples of the carboxylic acid isostere include, but are not limited to, an ester group-C(═O)OR^(20a), —SO₃H, —SO₂NHR^(19a), —B(OR^(m1))₂, —PO(OR^(m1))(OR^(m2)), —CONHR^(19a), —CONHSO₂R^(19a), —CONR^(19a)CN, —CONHNHSO₂R^(19a), and substituents represented by the formulas (8A), (8B), (8C), (8D), (8E), (8F), (8G), (8H), (8I), (8J), (8K), (8L), (8M), (8N), (8O), (8P), (8Q), (8R), (8S), (8T), (8U), (8V), and (8W) described below (each of the substituents is further optionally substituted with 1 to 3 of the same or different R^(19b) at a chemical substitutable position),

wherein [in (8V) and (8W),

R^(s) is a hydrogen atom, a C₁₋₆ alkyl group, or a C₃₋₁₀ alicyclic group (wherein the C₁₋₆ alkyl group or C₃₋₁₀ alicyclic group is optionally substituted with 1 to 5 halogen atoms),

R^(t) is a hydrogen atom, a C₁₋₆ alkyl group, a C₁₋₆ alkoxy group, (wherein the C₁₋₆ alkyl group or C₁₋₆ alkoxy group is optionally substituted with 1 to 5 halogen atoms), a C₃₋₁₀ alicyclic group, a C₃₋₁₀ alicyclic oxy group, a phenyl group, a phenoxy group, a pyridyl group, or a pyridyloxy group (wherein the C₃₋₁₀ alicyclic group, C₃₋₁₀ alicyclic oxy group, phenyl group, phenoxy group, pyridyl group, or pyridyloxy group is optionally substituted with 1 to 5 substituents selected from the group consisting of a halogen atom, a C₁₋₆ alkyl group, and a C₁₋₆ alkoxy group)],

R^(19a) and R^(19b) are the same or different, each independently representing a hydrogen atom, a hydroxyl group, a C₁₋₆ alkyl group, C₆₋₁₀ aryl, 5- or 6-membered heteroaryl, or a 4- to 10-membered non-aryl heterocycle,

R^(20a) is

1) a C₁₋₆ alkyl group, 2) a C₃₋₁₀ alicyclic group, 3) C₆₋₁₀ aryl, 4) 5- or 6-membered heteroaryl, or 5) a 4- to 10-membered non-aryl heterocycle, (wherein each substituent from 1) to 5) is optionally substituted),

R^(m1) represents

1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₁₀ alicyclic group, 4) C₆₋₁₀ aryl, 5) 5- or 6-membered heteroaryl, or 6) a 4- to 10-membered non-aryl heterocycle, (wherein each substituent from 2) to 6) is optionally substituted),

wherein if R^(m1) is attached to a boron atom via an oxygen atom, two R^(m1), as C₂₋₄ alkylene, together with the boron atom and two oxygen atoms, may form a 5- to 7-membered non-aryl heterocycle (wherein an alkylene moiety is optionally substituted in the non-aryl heterocycle), and

R^(m2) represents a hydrogen atom, an optionally substituted C₁₋₆ alkyl group, or an optionally substituted C₃₋₁₀ alicyclic group, wherein, preferably,

R^(s) is a hydrogen atom or a C₁₋₆ alkyl group, and

R^(t) is a hydrogen atom, a C₁₋₆ alkyl group, a C₁₋₆ alkoxy group, a C₃₋₁₀ alicyclic group, or a C₃₋₁₀ alicyclic oxy group, or alternatively preferably,

R^(19a) and R^(19b) are the same or different, each independently a hydrogen atom, a hydroxyl group, or a C₁₋₆ alkyl group, or also preferably

R^(m1) and R^(m2) are the same or different, each independently a hydrogen atom, a C₁₋₆ alkyl group, or a C₃₋₁₀ alicyclic group.

An example of an embodiment of the compounds of the invention includes a compound represented by formula (1a) or (1b):

or a pharmaceutically acceptable salt thereof, wherein

G is an oxygen atom, a sulfur atom, or —NR^(a1)—,

X is a hydroxyl group, an optionally substituted alkoxy group, or —NR^(a2)R^(b1),

R^(a1), R^(a2), and R^(b1) are the same or different, each independently a hydrogen atom, a hydroxyl group, an optionally substituted hydrocarbyl group, or an optionally substituted heterohydrocarbyl group,

wherein R^(a2) and R^(b1) together may form an optionally substituted nitrogen-containing non-aryl heterocycle,

L¹ is a single bond, an oxygen atom, a sulfur atom, —SO—, —SO₂—, an optionally substituted hydrocarbylene group, or an optionally substituted heterohydrocarbylene group,

L² is a single bond or an optionally substituted hydrocarbylene group,

Z is a hydrogen atom, a hydroxyl group, an optionally substituted hydrocarbyl group, or an optionally substituted heterohydrocarbyl group,

one of R¹, R², and R³ is represented by formula (2):

wherein

Y is an oxygen atom, a sulfur atom, or —NR^(j)—, and R^(j) is a hydrogen atom, a hydroxyl group, or an optionally substituted hydrocarbyl group,

ring A is an optionally substituted non-aryl heterocycle,

L³ is an oxygen atom, a sulfur atom, an optionally substituted hydrocarbylene group, an optionally substituted heterohydrocarbylene group, optionally substituted —NH—, optionally substituted —NH—SO₂—, —S(═O)—, or —S(═O)₂—,

L⁴ is a single bond, an optionally substituted hydrocarbylene group, an optionally substituted heterohydrocarbylene group, or —C(═N—OR^(h1))—,

R^(h1) is

1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₁₀ alicyclic group, 4) C₆₋₁₀ aryl, 5) 5- or 6-membered heteroaryl, or 6) a 4- to 10-membered non-aryl heterocycle, (wherein each substituent from 2) to 6) is optionally substituted),

R⁵ is a hydrogen atom, a hydroxyl group, an optionally substituted hydrocarbyl group, an optionally substituted heterohydrocarbyl group, optionally substituted —NHOH, a sulfo group (sulfonic acid group), optionally substituted —SO₂H, optionally substituted —SO₂—NH₂, optionally substituted —S(═O)(═NH)H, optionally substituted —NH—SO₂—H, optionally substituted —NH—SO₂—NH₂, optionally substituted —N═S(═O)H₂, or optionally substituted —NH₂,

the remaining two (without the structure of formula (2) among R¹, R², and R³) are the same or different, each independently a hydrogen atom, halogen, a hydroxyl group, an optionally substituted hydrocarbyl group, or an optionally substituted heterohydrocarbyl group,

R⁴ is

1) —C(═O)R⁸,

2) —SO₂-L⁶-R⁸, (wherein R⁸ in 1) and 2) is a hydroxyl group, an optionally substituted hydrocarbyl group, or an optionally substituted heterohydrocarbyl group, and L⁶ is a single bond or an optionally substituted hydrocarbylene group), 3) —NR^(a4)R^(b3), 4) —B(OR^(m1))₂, 5) —PO(OR^(m1))(OR^(m2)), 6) optionally substituted heteroaryl, 7) an optionally substituted non-aryl heterocycle, or 8) a bioisostere of one of 1) to 7), (wherein the formulas of 1), 2), 4), 5), and 6) include a carboxylic acid isostere, and 8) may include them in duplicates),

R^(a4) and R^(b3) are the same or different, each independently having the same definition as R^(a1), R^(a2), and R^(b1), wherein a combination of R^(a4) and R^(b3), when attached to the same nitrogen atom, together may form an optionally substituted nitrogen-containing non-aryl heterocycle,

R^(m1) is a hydrogen atom or an optionally substituted hydrocarbyl group,

wherein if R^(m1) is attached to a boron atom via an oxygen atom, two R^(m1), as alkylene, together with the boron atom and two oxygen atoms, may form a non-aryl heterocycle (wherein an alkylene moiety is optionally substituted in the non-aryl heterocycle),

R^(m2) is a hydrogen atom or an optionally substituted hydrocarbyl group, and

R⁶¹, R⁶², R⁶³, and R⁶⁴ are each independently a hydrogen atom, halogen, an optionally substituted alkyl group, or -L¹-L²-Z.

Another example of an embodiment of the compounds of the invention includes a compound represented by (1a) or (1b):

or a pharmaceutically acceptable salt thereof, wherein

G is an oxygen atom, a sulfur atom, or —NR^(a1)—,

X is a hydroxyl group, an optionally substituted alkoxy group, or —NR^(a2)R^(b1),

R^(a1), R^(a2), and R^(b1) are the same or different, each independently a hydrogen atom, a hydroxyl group, an optionally substituted hydrocarbyl group, or an optionally substituted heterohydrocarbyl group,

wherein R^(a2) and R^(b1) together may form an optionally substituted nitrogen-containing non-aryl heterocycle,

L¹ is a single bond, an oxygen atom, a sulfur atom, —SO—, —SO₂—, an optionally substituted hydrocarbylene group, or an optionally substituted heterohydrocarbylene group,

L² is a single bond or an optionally substituted hydrocarbylene group,

Z is a hydrogen atom, a hydroxyl group, an optionally substituted hydrocarbyl group, or an optionally substituted heterohydrocarbyl group,

one of R¹, R², and R³ is represented by formula (2):

wherein

Y is an oxygen atom, a sulfur atom, or —NR^(j)—, and R^(j) is a hydrogen atom, a hydroxyl group, or an optionally substituted hydrocarbyl group,

ring A is an optionally substituted non-aryl heterocycle,

L³ is an oxygen atom, a sulfur atom, an optionally substituted hydrocarbylene group, an optionally substituted heterohydrocarbylene group, —S(═O)— or —S(═O)₂—,

L⁴ is a single bond, an optionally substituted hydrocarbylene group, or —C(═N—OR^(h1))—,

R^(h1) is

1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₁₀ alicyclic group, 4) C₆₋₁₀ aryl, 5) 5- or 6-membered heteroaryl, or 6) a 4- to 10-membered non-aryl heterocycle, (wherein each substituent from 2) to 6) is optionally substituted),

R⁵ is a hydrogen atom, a hydroxyl group, an optionally substituted hydrocarbyl group, or an optionally substituted heterohydrocarbyl group,

the remaining two (without the structure of formula (2) among R¹, R², and R³) are the same or different, each independently a hydrogen atom, halogen, a hydroxyl group, an optionally substituted hydrocarbyl group, or an optionally substituted heterohydrocarbyl group,

R⁴ is

1) —C(═O)R⁸,

2) —SO₂-L⁶-R⁸, (wherein R⁸ in 1) and 2) is a hydroxyl group, an optionally substituted hydrocarbyl group, or an optionally substituted heterohydrocarbyl group, and L⁶ is a single bond or an optionally substituted hydrocarbylene group), 3) —NR^(a4)R^(b3), 4) —B(OR^(m1))₂, 5) —PO(OR^(m1))(OR^(m2)), 6) optionally substituted heteroaryl, 7) an optionally substituted non-aryl heterocycle, or 8) a bioisostere of one of 1) to 7), (wherein the formulas of 1), 2), 4), 5), and 6) include a carboxylic acid isostere, and 8) may include them in duplicates),

R^(a4) and R^(b3) are the same or different, each independently having the same definition as R^(a1), R^(a2), and R^(b1), wherein a combination of R^(a4) and R^(b3), when attached to the same nitrogen atom, together may form an optionally substituted nitrogen-containing non-aryl heterocycle,

R^(m1) is a hydrogen atom or an optionally substituted hydrocarbyl group,

wherein if R^(m1) is attached to a boron atom via an oxygen atom, two R^(m1), as alkylene, together with the boron atom and two oxygen atoms, may form a non-aryl heterocycle (wherein an alkylene moiety is optionally substituted in the non-aryl heterocycle),

R^(m2) is a hydrogen atom or an optionally substituted hydrocarbyl group, and

R⁶¹, R⁶², R⁶³, and R⁶⁴ are each independently a hydrogen atom, halogen, an optionally substituted alkyl group, or -L¹-L²-Z.

In some embodiments, in formula (1a) or (1b),

G is an oxygen atom, a sulfur atom, or —NR^(a1)—,

X is a hydroxyl group, an optionally substituted C₁₋₆ alkoxy group, or —NR^(a2)R^(b1),

R^(a1), R^(a2), and R^(b1) are the same or different, each independently

1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₁₀ alicyclic group, 4) C₆₋₁₀ aryl 5) 5- or 6-membered heteroaryl, 6) a 4- to 10-membered non-aryl heterocycle, 7) a C₁₋₆ alkylcarbonyl group, 8) a C₃₋₁₀ alicyclic carbonyl group, 9) a C₆₋₁₀ arylcarbonyl group, 10) a 5- or 6-membered heteroarylcarbonyl group, 11) a C₁₋₆ alkylsulfonyl group, 12) a C₃₋₁₀ alicyclic sulfonyl group, 13) a C₆₋₁₀ arylsulfonyl group, 14) a 5- or 6-membered heteroarylsulfonyl group, or

15) —OR^(c1),

(wherein each substituent from 2) to 14) is optionally substituted),

wherein R^(a2) and R^(b1), together may form an optionally substituted 4- to 10-membered nitrogen-containing non-aryl heterocycle,

R^(c1) is

1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₁₀ alicyclic group, 4) C₆₋₁₀ aryl, 5) 5- or 6-membered heteroaryl, or 6) a 4- to 10-membered non-aryl heterocycle, (wherein each substituent from 2) to 6) is optionally substituted),

L¹ is a single bond, an oxygen atom, a sulfur atom, —SO—, —SO₂—, —NR^(d1)—, —NR^(d1)(═O)—, or —NR^(d1)SO₂—,

L² is a single bond or an optionally substituted C₁₋₆ alkylene group,

Z is

1) a hydrogen atom, 2) a hydroxyl group, 3) a cyano group, 4) a carboxyl group, 5) a C₃₋₁₀ alicyclic group, 6) C₆₋₁₀ aryl, 7) 5- or 6-membered heteroaryl, 8) a 4- to 10-membered non-aryl heterocycle, 9) a C₁₋₆ alkoxy group, 10) a C₃₋₁₀ alicyclic oxy group, 11) a C₆₋₁₀ aryloxy group, 12) a 5- or 6-membered heteroaryloxy group, 13) a 4- to 10-membered non-aryl heterocyclyl oxy group, 14) a C₁₋₆ alkylthio group, 15) a C₃₋₁₀ alicyclic thio group, 16) a C₆₋₁₀ arylthio group, 17) a 5- or 6-membered heteroarylthio group, 18) a 4- to 10-membered non-aryl heterocyclyl thio group, (wherein each substituent from 5) to 18) is optionally substituted), 19) —SO₂—NR^(e1)R^(f1), 20) —NR^(e1)—C(═O)OR^(f1), 21) —NR^(g1)—C(═O)NR^(e1)R^(f1), 22) —NR^(e1)—C(═S)R^(f1), 23) —NR^(e1)—C(═S)OR^(f1), 24) —NR^(g1)—C(═S)NR^(e1)R^(f1), 25) —NR^(g1)—CR^(e1)(═NR^(f1)), 26) —NR^(g1)—CR^(e1)(═N—OR^(f1)), 27) —NR^(h1)—C(═NR^(g1))NR^(e1)R^(f1), 28) —NR^(h1)—C(═N—OR^(g1))NR^(e1)R^(f1), 29) —NR^(i1)—C(═NR^(h1))NR^(g1)—NR^(e1)R^(f1), 30) —NR^(i1)—C(═N—OR^(h1))NR^(g1)—NR^(e1)R^(f1), 31) —NR^(e1)—SO₂—R^(f1), 32) —NR^(g1)—SO₂—NR^(e1)R^(f1),

33) —C(═O)OR^(e1), 34) —C(═S)OR^(e1),

35) —C(═S)NR^(e1)R^(f1), 36) —C(═S)NR^(e1)OR^(f1), 37) —C(═S)NR^(g1)—NR^(e1)R^(f1), 38) —C(═NR^(e1))R^(f1), 39) —C(═N—OR^(e1))R^(f1), 40) —C(═NR^(h1))NR^(g1)—NR^(e1)R^(f1), 41) —C(═N—OR^(h1))NR^(g1)—NR^(e1)R^(f1), 42) —NR^(e1)R^(f1), 43) —NR^(g1)—NR^(e1)R^(f1), 44) —NR^(e1)OR^(f1), 45) —NR^(e1)—C(═O)R^(f1), 46) —C(═O)NR^(e1)R^(f1), 47) —C(═O)NR^(e1)OR^(f1), 48) —C(═O)NR^(g1)—NR^(e1)R^(f1),

49) —C(═O)R^(e1),

50) —C(═NR^(g1))NR^(e1)R^(f1), or 51) —C(═N—OR^(h1))NR^(e1)R^(f1),

one of R¹, R², and R³ is a group represented by formula (2):

wherein

Y is an oxygen atom, a sulfur atom, or —NR^(j)—,

ring A is an optionally substituted 4- to 20-membered non-aryl heterocycle,

L³ is

1) an oxygen atom, 2) a sulfur atom,

3) —NR^(d2)—, 4) —NR^(d2)(═O)—,

5) —NR^(d2)SO₂—, 6) a C₁₋₆ alkylene group, 7) a C₃₋₁₀ cycloalkylene group, 8) a 4- to 10-membered non-aryl heterocyclylene group, (wherein each substituent from 6) to 8) is optionally substituted),

9) —C(═O)—, 10) —S(═O)—, or 11) —S(═O)₂—,

L⁴ is

1) a single bond, 2) a C₁₋₆ alkylene group, 3) a C₃₋₁₀ cycloalkylene group, 4) a C₆₋₁₀ arylene group, 5) a 5- or 6-membered heteroarylene group, 6) a 4- to 10-membered non-aryl heterocyclylene group, (wherein each substituent from 2) to 6) is optionally substituted), or

7) —C(═N—OR^(h1))—,

R⁵ is

1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₁₀ alicyclic group, 4) a 4- to 10-membered non-aryl heterocycle, 5) C₆₋₁₀ aryl, 6) 5- to 10-membered heteroaryl, 7) a C₁₋₆ alkylthio group, (wherein each substituent from 2) to 7) is optionally substituted, and if two substituents further substituted with the substituent of 1), 2), or 3) are each substituted on adjacent atoms within a ring, the two substituents together may further form a condensed ring structure),

8) —NR^(e1)OH,

9) a carboxyl group (—C(═O)OH) 10) a carboxylic acid isostere (wherein the carboxylic acid isostere comprises an ester group-C(═O)OR^(20a)), 11) a sulfo group (sulfonic acid group), 12) —SO₂R^(e1), 13) —SO₂—NR^(e1)R^(f1), 14) —S(═O)(═NR^(f1))R^(e1), 15) —NR^(e1)—C(═O)R^(f1), 16) —NR^(e1)—C(═O)OR^(f1), 17) —NR^(g1)—C(═O)NR^(e1)R^(f1), 18) —NR^(e1)—SO₂—R^(f1), 19) —NR^(g1)—SO₂—NR^(e1)R^(f1), 20) —N═S(═O)R^(e1)R^(f1), 21) —C(═O)NR⁵⁰R⁵¹, or 22) —NR^(e1)R^(f1) (wherein if R⁵ is the substituent of 22), -L³-L⁴-R⁵ is not —(CH₂)₁₋₄NR^(e1), R^(f1) (wherein R^(e1) and R^(f1) are a hydrogen atom, optionally substituted C₁₋₄ alkyl, an optionally substituted C₃₋₇ alicyclic group, an optionally substituted 4- to 10-membered non-aryl heterocyclic group, optionally substituted C₆₋₁₀ aryl, or optionally substituted 5- to 10-membered heteroaryl)),

R^(20a) is

1) a C₁₋₆ alkyl group, 2) a C₃₋₁₀ alicyclic group, 3) C₆₋₁₀ aryl, 4) 5- or 6-membered heteroaryl, or 5) a 4- to 10-membered non-aryl heterocycle, (wherein each substituent from 1) to 5) is optionally substituted),

R⁵⁰ represents

1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a hydroxyl group, 4) a C₁₋₆ alkoxy group, 5) a C₃₋₆ cycloalkoxy group, 6) a C₃₋₆ alicyclic group, 7) a 4- to 6-membered non-aryl heterocycle, 8) C₆₋₁₀ aryl, 9) 5- to 10-membered heteroaryl, 10) a 4- to 6-membered non-aryl heterocyclyl oxy, 11) C₆₋₁₀ aryloxy, 12) 5- to 10-membered heteroaryloxy, 13) a C₁₋₆ alkylsulfonyl group, 14) a C₃₋₆ cycloalkoxysulfonyl group, or 15) a 4- to 6-membered non-aryl heterocyclyl sulfonyl group, (wherein each substituent of 2) and 4) to 15) is optionally substituted),

R⁵¹ represents

1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₆ alicyclic group, 4) a 4- to 6-membered non-aryl heterocycle, 5) C₆₋₁₀ aryl, or 6) 5- to 10-membered heteroaryl, (wherein each substituent from 2) to 6) is optionally substituted), or

R⁵⁰ and R⁵¹ together may form an optionally substituted 4- to 7-membered nitrogen-containing non-aryl heterocycle,

the remaining two (without the structure of formula (2) among R¹, R², and R³) are the same or different, each independently a hydrogen atom, a halogen atom, an optionally substituted C₁₋₆ alkyl group, an optionally substituted C₁₋₆ alkoxy group, an optionally substituted C₁₋₆ alkylthio group, optionally substituted 5- or 6-membered heteroaryl, or —NR^(a3)R^(b2),

R^(d1), R^(d2), R^(e1), R^(f1), R^(g1), R^(h1), R^(i1), and R^(j) are the same or different, each independently

1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₁₀ alicyclic group, 4) C₆₋₁₀ aryl, 5) 5- or 6-membered heteroaryl, or 6) a 4- to 10-membered non-aryl heterocycle, (wherein each substituent from 2) to 6) is optionally substituted),

a combination of R^(e1) and R^(f1), when attached to the same nitrogen atom, together may form an optionally substituted 4- to 10-membered nitrogen-containing non-aryl heterocycle,

R⁴ is

1) —C(═O)R⁸,

2) —SO₂-L⁶-R⁸, (wherein R⁸ in 1) and 2) is —NR^(a5)R^(b4), —NR^(a5)-L⁷-B(OR^(m1))₂, —OR^(m1), or an optionally substituted C₁₋₆ alkyl group, and L⁶ is a single bond or —NR^(a6)—), 3) —NR^(a4)R^(b3), 4) —B(OR^(m1))₂, 5) —PO(OR^(m1))(OR^(m2)), 6) optionally substituted 5-membered heteroaryl, 7) an optionally substituted 5-membered non-aryl heterocycle, or 8) a bioisostere of one of 1) to 7), (wherein the formulas of 2), 4), 5), and 6) include a carboxylic acid isostere, and 8) may include them in duplicates),

R^(a3), R^(a4), R^(a5), R^(a6), R^(b2), R^(b3), and R^(b4) are the same or different, each independently having the same definition as R^(a1), R^(a2), and R^(b1), wherein a combination of R^(a3) and R^(b2), R^(a4) and R^(b3), or R^(a5) and R^(b4), when attached to the same nitrogen atom, together may form an optionally substituted 4- to 10-membered nitrogen-containing non-aryl heterocycle,

R^(m1) is

1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₁₀ alicyclic group, 4) C₆₋₁₀ aryl, 5) 5- or 6-membered heteroaryl, or 6) a 4- to 10-membered non-aryl heterocycle, (wherein each substituent from 2) to 6) is optionally substituted),

wherein if R^(m1) is attached to a boron atom via an oxygen atom, two R^(m1), as C₂₋₄ alkylene, together with the boron atom and two oxygen atoms, may form a 5- to 7-membered non-aryl heterocycle (wherein an alkylene moiety is optionally substituted in the non-aryl heterocycle),

R^(m2) is a hydrogen atom, an optionally substituted C₁₋₆ alkyl group, or an optionally substituted C₃₋₁₀ alicyclic group,

L⁷ is an optionally substituted C₁₋₃ alkylene group,

R⁶¹, R⁶², and R⁶³ are each independently a hydrogen atom, halogen or an optionally substituted C₁₋₆ alkyl group, and

R⁶⁴ is a hydrogen atom, halogen, an optionally substituted C₁₋₆ alkyl group, or -L¹-L²-Z.

In some embodiments, L³ is

1) a C₁₋₆ alkylene group, 2) a C₃₋₁₀ cycloalkylene group, or 3) a 4- to 10-membered non-aryl heterocyclylene group, (wherein each substituent from 1) to 3) is optionally substituted), and

L⁴ is a single bond or an optionally substituted C₁₋₅ alkylene group.

In some embodiments, L³ is an optionally substituted C₁₋₄ alkylene group, and

L⁴ is a single bond or an optionally substituted C₁₋₃ alkylene group.

In some embodiments, L³ is —(CR³⁰R³¹)_(n1)—,

R³⁰ and R³¹ each independently, or if there are multiple instances of each of them, all of them independently represent

1) a hydrogen atom, 2) —NR^(a7)R^(a8), 3) a C₁₋₄ alkyl group, 4) C₆₋₁₀ aryl, 5) 5- to 10-membered heteroaryl, 6) a C₃₋₆ alicyclic group, 7) a 4- to 10-membered non-aryl heterocycle, (wherein each substituent from 3) to 7) is optionally substituted), or

8) —OR^(c2), or

R³⁰ and R³¹, together with the carbon atom to which they are attached, form a C₃₋₆ alicyclic group or a 4- to 6-membered non-aryl heterocycle,

R^(a7) and R^(a8) are the same or different, each independently

1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₁₀ alicyclic group, 4) C₆₋₁₀ aryl 5) 5- or 6-membered heteroaryl, 6) a 4- to 10-membered non-aryl heterocycle, 7) a C₁₋₆ alkylcarbonyl group, 8) a C₃₋₁₀ alicyclic carbonyl group, 9) a C₆₋₁₀ arylcarbonyl group, 10) a 5- or 6-membered heteroarylcarbonyl group, 11) a C₁₋₆ alkylsulfonyl group, 12) a C₃₋₁₀ alicyclic sulfonyl group, 13) a C₆₋₁₀ arylsulfonyl group, 14) a 5- or 6-membered heteroarylsulfonyl group, or

15) —OR^(c3)

(wherein each substituent from 2) to 14) is optionally substituted),

wherein R^(a7) and R^(a8) together may form an optionally substituted 4- to 10-membered nitrogen-containing non-aryl heterocycle,

R^(c2) and R^(c3) are each independently,

1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₁₀ alicyclic group, 4) C₆₋₁₀ aryl, 5) 5- or 6-membered heteroaryl, or 6) a 4- to 10-membered non-aryl heterocycle, (wherein each substituent from 2) to 6) is optionally substituted),

n1 is an integer 1, 2, 3, or 4,

L⁴ is —(CR⁴⁰R⁴¹)_(n2)—,

R⁴⁰ and R⁴¹ each independently, or if there are multiple instances of each of them, all of them independently represent

1) a hydrogen atom, 2) —NR^(a9)R^(a10), 3) a C₁₋₄ alkyl group, 4) C₆₋₁₀ aryl, 5) 5- to 10-membered heteroaryl, 6) a C₃₋₆ alicyclic group, 7) a 4- to 10-membered non-aryl heterocycle, (wherein each substituent from 3) to 7) is optionally substituted), or

8) —OR^(c4), or

R⁴⁰ and R⁴¹, together with the carbon atom to which they are attached, form a C₃₋₆ alicyclic group or a 4- to 6-membered non-aryl heterocycle,

R^(a9) and R^(a10) are the same or different, each independently

1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₁₀ alicyclic group, 4) C₆₋₁₀ aryl 5) 5- or 6-membered heteroaryl, 6) a 4- to 10-membered non-aryl heterocycle, 7) a C₁₋₆ alkylcarbonyl group, 8) a C₃₋₁₀ alicyclic carbonyl group, 9) a C₆₋₁₀ arylcarbonyl group, 10) a 5- or 6-membered heteroarylcarbonyl group, 11) a C₁₋₆ alkylsulfonyl group, 12) a C₃₋₁₀ alicyclic sulfonyl group, 13) a C₆₋₁₀ arylsulfonyl group, 14) a 5- or 6-membered heteroarylsulfonyl group, (wherein each substituent from 2) to 14) is optionally substituted), or

15) —OR^(c5),

wherein R^(a9) and R^(a10) together may form an optionally substituted 4- to 10-membered nitrogen-containing non-aryl heterocycle,

R^(c4) and R^(c5) are each independently defined the same as R^(c2) and R^(c3), and

n2 is an integer 0 (i.e., when L⁴ is a single bond), 1, 2, or 3.

In some embodiments, -L³-L⁴- is an optionally substituted C₁₋₂ alkylene group.

In some embodiments, -L³-L⁴- is a C₁₋₂ alkylene group optionally substituted with a C₁₋₃ alkyl group, an amino group, or a hydroxymethyl group, or a plurality of the same or different groups thereamong (wherein two C₁₋₃ alkyl groups, when attached to the same carbon atom, together with the carbon atom to which they are attached, may form a C₃₋₆ alicyclic group).

R⁵ is

1) a C₃₋₁₀ alicyclic group, 2) C₆₋₁₀ aryl, 3) 5- to 10-membered heteroaryl, 4) a C₁₋₆ alkylthio group, (wherein each substituent from 1) to 4) is optionally substituted, and if two substituents further substituted with the substituent of 2) or 3) are each substituted on adjacent atoms within a ring, the two substituents together may further form a condensed ring structure),

5) —NR^(e1)OH,

6) —C(═O)NR⁵⁰R⁵¹, 7) —SO₂—NR^(e1)R^(f1), 8) —NR^(e1)—SO₂—R^(f1),

9) —C(═O)OR²⁰, or

10) —NR^(e1)R^(f1) (wherein if R⁵ is the substituent of 10), L³ and/or L⁴ is a C₁₋₆ alkylene group that is necessarily substituted with one or more groups other than a hydrogen atom (wherein L³ or L⁴, together with said substituent, may form a C₃₋₁₀ alicyclic group or a 4- to 10-membered non-aryl heterocycle)), and

R²⁰ is

1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₁₀ alicyclic group, 4) C₆₋₁₀ aryl, 5) 5- or 6-membered heteroaryl, or 6) a 4- to 10-membered non-aryl heterocycle, (wherein each substituent from 2) to 6) is optionally substituted)

In some embodiments, R⁵ is

1) C₆₋₁₀ aryl, 2) 5- to 10-membered heteroaryl, 3) —C(═O)NR⁵⁰R⁵¹,

4) —C(═O)OR²⁰, or

5) —NR^(e1)R^(f1) (wherein if R⁵ is the substituent of 5), L³ and/or L⁴ is a C₁₋₆ alkylene group that is necessarily substituted with one or more groups other than a hydrogen atom, and together with said substituent forms at least one C₃₋₁₀ alicyclic group or 4- to 10-membered non-aryl heterocycle) (wherein each substituent from 1) to 2) is optionally substituted, and any two groups thereof, when each is attached to adjacent atoms within a ring, together may further form a condensed ring structure).

In some embodiments, Z-L²-L¹ is an optionally substituted C₁₋₆ alkylthio group.

In some embodiments, R⁶¹, R⁶², R⁶³, and R⁶⁴ are each independently a hydrogen atom, a fluorine atom, or a C₁₋₃ alkyl group optionally substituted with a fluorine atom.

In some embodiments, R⁶¹, R⁶², R⁶³, and R⁶⁴ are each independently a hydrogen atom or a fluorine atom.

In some embodiments, G is an oxygen atom.

In some embodiments, X is a hydroxyl group or an optionally substituted C₁₋₆ alkoxy group.

In some embodiments, X is a hydroxyl group.

In some embodiments, R⁴ is

1) —C(═O)OH (i.e., a carboxyl group), or 2) a carboxylic acid isostere.

In some embodiments, ring A is an optionally substituted 4- to 20-membered non-aryl heterocycle. In some embodiments, ring A is an optionally substituted 4- to 10-membered non-aryl heterocycle. In some embodiments, ring A is an optionally substituted 4- to 7-membered non-aryl heterocycle. In some embodiments, ring A is an optionally substituted 4- to 7-membered nitrogen-containing non-aryl heterocycle. In a certain embodiment, ring A is

wherein m is 1, 2, or 3, n is 1, 2, or 3, m+n is 2, 3, 4, or 5, a bond that is orthogonal to a wavy line indicates a bond with Y, and a bond with * indicates a bond with L³. In some embodiments, m+n is 2, 3, or 4.

In some embodiments, ring A is an optionally substituted 4- to 6-membered non-aryl heterocycle. In some embodiments, ring A is an optionally substituted 4- to 6-membered nitrogen-containing non-aryl heterocycle.

In some embodiments, ring A is

wherein m+n is 2 or 3. In a preferred embodiment, m+n is 2. In a more preferred embodiment, m=1 and n=1.

In some embodiments, m is 1 or 2, n is 1 or 2, and m+n is 2 or 3. In some embodiments, m is 1, and n is 1.

In some embodiments, ring A is an optionally substituted azetidine ring. In a certain embodiment in such embodiments, ring A is

wherein R²⁶ represents a substituent on an azetidine ring and is defined the same as R^(6a), a bond that is orthogonal to a wavy line indicates a bond with Y, and a bond with * indicates a bond with L³. In a preferred embodiment, R²⁶ are the same or different, each independently selected from the group consisting of 1) a hydrogen atom, 2) a halogen atom, 3) a C₁₋₆ alkyl group, and 4) a C₁₋₆ alkoxy group, (wherein each of substituents 3) and 4) is optionally substituted with a halogen atom) (wherein a halogen atom in 2), 3), and 4) is more preferably a fluorine atom), and in a more preferred embodiment, are selected from the group consisting of 1) a hydrogen atom, 2) a halogen atom, and 3) a C₁₋₆ alkyl group optionally substituted with a halogen atom, (wherein a halogen atom in 2) and 3) is more preferably a fluorine atom), and most preferably are hydrogen atoms.

In some embodiments, Y is an oxygen atom or a sulfur atom. In some embodiments, Y is an oxygen atom.

In some embodiments, L³ is —C(═O)— or —S(═O)₂—. In some embodiments, L³ is —C(═O)—.

In some embodiments, L⁴ is a single bond, —C(═N—OR^(h1))—, or an optionally substituted C₁₋₆ alkylene group, wherein R^(h1) is an optionally substituted C₁₋₆ alkyl group.

In some embodiments, R¹ and R² are the same or different, each independently selected from the group consisting of

1) a hydrogen atom, 2) a halogen atom, 3) a C₁₋₆ alkyl group, 4) a C₁₋₆ alkoxy group, and 5) a C₁₋₆ alkylthio group, (wherein each substituent from 3) to 5) is optionally substituted)

In some embodiments, R¹ and R² are the same or different, each independently selected from the group consisting of

1) a hydrogen atom, 2) a halogen atom, 3) a C₁₋₆ alkyl group, 4) a C₁₋₆ alkoxy group, and 5) a C₁₋₆ alkylthio group, (wherein each substituent from 3) to 5) is optionally substituted with a halogen atom).

In some embodiments, R¹ and R² are the same or different, each independently selected from the group consisting of

1) a hydrogen atom, 2) a halogen atom, 3) a C₁₋₆ alkyl group optionally substituted with a halogen atom.

In some embodiments, R¹ and R² are the same or different, each independently selected from the group consisting of

1) a hydrogen atom, 2) a fluorine atom, 3) a C₁₋₃ alkyl group optionally substituted with a fluorine atom.

In some embodiments, R¹ and R² are both hydrogen atoms.

In some embodiments, L³ is —(CR³⁰R³¹)_(n1)— or 4- to 10-membered non-aryl heterocyclylene,

R³⁰ and R³¹ each independently, or if there are multiple instances of each of them, all of them independently represent

1) a hydrogen atom, 2) an optionally substituted C₁₋₄ alkyl group, or 3) optionally substituted C₆₋₁₀ aryl,

n1 is 1, 2, or 3,

L⁴ is a single bond or —(CR⁴⁰R⁴¹)_(n2)—,

R⁴⁰ and R⁴¹ each independently, or if there are multiple instances of each of them, all of them independently represent

1) a hydrogen atom, 2) —NR^(a9)R^(a10), 3) an optionally substituted C₁₋₄ alkyl group, or

4) —OR^(c4), or

R⁴⁰ and R⁴¹, together with the carbon atom to which they are attached, form a C₃₋₆ alicyclic group or a 4- to 6-membered non-aryl heterocycle,

R^(a9), R^(a10), and R^(c4) are the same or different, each independently

1) a hydrogen atom, 2) an optionally substituted C₁₋₆ alkyl group, or 3) an optionally substituted C₃₋₁₀ alicyclic group,

wherein R^(a9) and R^(a10) together may form an optionally substituted 4- to 10-membered nitrogen-containing non-aryl heterocycle, and

n2 is 0, 1, or 2.

In some embodiments, L³ is —(CR³⁰R³¹)_(n1)—,

R³⁰ and R³¹ each independently, or if there are multiple instances of each of them, all of them independently represent

1) a hydrogen atom, 2) an optionally substituted C₁₋₄ alkyl group, or 3) optionally substituted C₆₋₁₀ aryl,

n1 is 1, 2, or 3,

L⁴ is —(CR⁴⁰R⁴¹)_(n2)—,

R⁴⁰ and R⁴¹ each independently, or if there are multiple instances of each of them, all of them independently represent

1) a hydrogen atom, 2) —NR^(a9)R^(a10), 3) an optionally substituted C₁₋₄ alkyl group, or

4) —OR^(c4), or

R⁴⁰ and R⁴¹, together with the carbon atom to which they are attached, form a C₃₋₆ alicyclic group or a 4- to 6-membered non-aryl heterocycle,

R^(a9), R^(a10), and R^(c4) are the same or different, each independently

1) a hydrogen atom, 2) an optionally substituted C₁₋₆ alkyl group, or 3) an optionally substituted C₃₋₁₀ alicyclic group,

wherein R^(a9) and R^(a10) together may form an optionally substituted 4- to 10-membered nitrogen-containing non-aryl heterocycle, and

n2 is 0, 1, or 2.

In some embodiments, n1 is 1 or 2, and n2 is 0 or 1.

In some embodiments, L³ is —CR³⁰R³¹— or 4- to 10-membered non-aryl heterocyclylene,

R³⁰ and R³¹ each independently represent,

1) a hydrogen atom, 2) a C₁₋₄ alkyl group (wherein the group is optionally substituted with halogen, —NR^(a11)R^(a12), or —OR^(c6)), or 3) C₆ aryl (wherein the group is optionally substituted with halogen, —NR^(a13)R^(a14), —OR^(c7), or a C₁₋₃ alkyl group (wherein the group is optionally substituted with halogen, —NR^(a15)R^(a16), or —OR^(c8))),

L⁴ is a single bond or —(CR⁴⁰R⁴¹)_(n2)—,

R⁴⁰ and R⁴¹ each independently represent,

1) a hydrogen atom, 2) —NR^(a9)R^(a10), 3) a C₁₋₄ alkyl group (wherein the group is optionally substituted with halogen, —NR^(a17)R^(a18), or —OR^(c9)), or

4) —OR^(c4), or

R⁴⁰ and R⁴¹, together with the carbon atom to which they are attached, form a C₃₋₆ alicyclic group,

R^(a9), R^(a10), R^(a11), R^(a12), R^(a13), R^(a14), R^(a15), R^(a16), R^(a17), R^(a18), R^(c4), R^(c6), R^(c7), R^(c8), and R^(c9) are the same or different, each independently representing

1) a hydrogen atom, or 2) a C₁₋₄ alkyl group (wherein the group is optionally substituted with halogen, —NR^(a19)R^(a20), or —OR^(c10)),

R^(a19), R^(a20), and R^(c10) are the same or different, each independently representing

1) a hydrogen atom, or 2) a C₁₋₄ alkyl group (wherein the group is optionally substituted with halogen),

wherein each combination of R^(a9) and R^(a10), Rau and R^(a12), R^(a13) and R^(a14), R^(a15) and R^(a16), R^(a17) and R^(a18), or R^(a19) and R^(a20) together may form an optionally substituted 4- to 7-membered nitrogen-containing non-aryl heterocycle, and

n2 is 0 or 1.

In some embodiments, L³ is —CR³⁰R³¹—,

R³⁰ and R³¹ each independently represent,

1) a hydrogen atom, 2) a C₁₋₄ alkyl group (wherein the group is optionally substituted with halogen, —NR^(a11)R^(a12), or —OR^(c6)), or 3) C₆ aryl (wherein the group is optionally substituted with halogen, —NR^(a13)R^(a14), —OR^(c7), or a C₁₋₃ alkyl group (wherein the group is optionally substituted with halogen, —NR^(a15)R^(a16), or —OR^(c8))),

L⁴ is —(CR⁴⁰R⁴¹)_(n2)—,

R⁴⁰ and R⁴¹ each independently represent,

1) a hydrogen atom, 2) —NR^(a9)R^(a10), 3) a C₁₋₄ alkyl group (wherein the group is optionally substituted with halogen, —NR^(a17)R^(a18), or —OR^(c9)), or

4) —OR^(c4), or

R⁴⁰ and R⁴¹, together with the carbon atom to which they are attached, form a C₃₋₆ alicyclic group,

R^(a9), R^(a10), R^(a11), R^(a12), R^(a13), R^(a14), R^(a15), R^(a16), R^(a17), R^(a18), R^(c4), R^(c6), R^(c7), R^(c8), and R^(c9) are the same or different, each independently representing

1) a hydrogen atom or 2) a C₁₋₄ alkyl group (wherein the group is optionally substituted with halogen, —NR^(a19)R^(a20), or —OR^(c10)),

R^(a19), R^(a20), and R^(c10) are the same or different, each independently representing

1) a hydrogen atom, or 2) a C₁₋₄ alkyl group (wherein the group is optionally substituted with halogen),

wherein each combination of R^(a9) and R^(a10), R^(a11) and R^(a12), R^(a13) and R^(a14), R^(a15) and R^(a16), R^(a17) and R^(a18), or R^(a19) and R^(a20) together may form an optionally substituted 4- to 7-membered nitrogen-containing non-aryl heterocycle, and

n2 is 0 or 1.

In some embodiments,

L³ is —CH₂—, —CH(CH₂NH₂)—, or —CH(CH₂OH)—, and

L⁴ and a single bond, —CH₂—, —CH(NH₂)—, —CMe(NH₂)—, —CEt(NH₂)—, —C(iso-Pr)(NH₂)—, —CH(CH₂NH₂)—, —CH(OH)—, —CH(CH₂OH)—, —C(CH₂OH)₂—, or

In some embodiments,

L³ is —CH₂—, —CH(CH₂NH₂)—, or —CH(CH₂OH)—, and

L⁴ is a single bond, —CH₂—, —CH(NH₂)—, —CMe(NH₂)—, —CEt(NH₂)—, —C(iso-Pr)(NH₂)—, —CH(CH₂NH₂)—, —CH(OH)—, —CH(CH₂OH)—, or

In some embodiments, L³ is 4- to 10-membered non-aryl heterocyclylene.

In some embodiments, L³ is 5-membered non-aryl heterocyclylene.

In some embodiments, L³ is

In some embodiments, L⁴ is a single bond.

In some embodiments, R⁵ is

1) C₆₋₁₀ aryl, or 2) 5- to 10-membered heteroaryl, (wherein each substituent from 1) to 2) is optionally substituted, and if two substituents further substituted with the substituent of 1) or 2) are each substituted on adjacent atoms within a ring, the two substituents together may further form a condensed ring structure).

In some embodiments, R⁵ is C₆ aryl (i.e., phenyl) or 5-membered, 6-membered, 9-membered, or 10-membered heteroaryl,

each group of R⁵ is optionally substituted with each of R^(6a) or R^(6b) at all chemically substitutable positions on a carbon atom or a nitrogen atom within a ring thereof,

wherein R^(6a), which are substituents on the carbon atom, if there are multiple instances on the same ring, are all independently selected from the group consisting of

1) a hydrogen atom, 2) a hydroxyl group, 3) a cyano group, 4) halogen, 5) a C₁₋₄ alkyl group, 6) a C₃₋₁₀ alicyclic group, 7) a C₁₋₄ alkoxy group, 8) a C₃₋₁₀ alicyclic oxy group, 9) a C₆₋₁₀ aryloxy group, 10) a 5- or 6-membered heteroaryloxy group, 11) a 4- to 10-membered non-aryl heterocyclyl oxy group, (wherein each substituent from 5) and 11) is optionally substituted), 12) —SO₂—NR^(e2)R^(f2), 13) —NR^(g2)—CR^(e2)(═NR^(f2)), 14) —NR^(g2)—CR^(e2)(═N—OR^(f2)), 15) —NR^(h2)—C(═NR^(g2))NR^(e2)R^(f2), 16) —NR^(h2)—C(═N—OR^(g2))NR^(e2)R^(f2), 17) —NR^(i2)—C(═NR^(h2))NR^(g2)—NR^(e2)R^(f2), 18) —NR^(i2)—C(═N—OR^(h2))NR^(g2)—NR^(e2)R^(f2), 19) —C(═NR^(e2))R^(f2), 20) —C(═N—OR^(e2))R^(f2), 21) —C(═NR^(h2))—NR^(e2)R^(f2), 22) —C(═NR^(h2))NR^(g2)—NR^(e2)R^(f2), 23) —C(═N—OR^(h2))NR^(g2)—NR^(e2)R^(f2), 24) —NR^(e2)R^(f2), 25) —NR^(g2)—NR^(e2)R^(f2), 26) —NR^(e2)OR^(f2), 27) —NR^(e2)—C(═O)R^(f2), 28) —C(═O)NR^(e2)R^(f2), 29) —C(═O)NR^(e2)OR^(f2), 30) —C(═O)NR^(g2)—NR^(e2)R^(f2),

31) —C(═O)R^(e2), 32) —C(═O)OR^(e2), and

33) —C(═N—OR^(h2))NR^(e2)R^(f2),

wherein R^(6b), which are substituents on the nitrogen atom, if there are multiple instances on the same ring, are all independently selected from the group consisting of

1) a hydrogen atom, 2) a hydroxyl group, 3) a C₁₋₄ alkyl group (wherein the alkyl group is optionally substituted), 4) a C₃₋₁₀ alicyclic group (wherein the alicyclic group is optionally substituted), 5) —C(═NR^(e2))R^(f2), 6) —C(═N—OR^(e2))R^(f2), 7) —SO₂—NR^(e2)R^(f2), 8) —C(═NR^(h2))—NR^(e2)R^(f2), 9) —C(═NR^(h2))NR^(g2)—NR^(e2)R^(f2), 10) —C(═N—OR^(h2))NR^(g2)—NR^(e2)R^(f2), 11) —C(═O)NR^(e2)R^(f2), 12) —C(═O)NR^(e2)OR^(f2), 13) —C(═O)NR^(g2)—NR^(e2)R^(f2),

14) —C(═O)R^(e2), and

15) —C(═N—OR^(h2))NR^(e2)R^(f2), or

if a combination of two R^(6a) or R^(6a) and R^(6b) are each substituted on adjacent atoms within a ring, the two substituents together may form an optionally substituted 5- to 6-membered heteroaryl ring or an optionally substituted 5- to 7-membered non-aryl heterocycle, which further fuses to an attachment moiety between the adjacent atoms within the ring,

R^(e2), R^(f2), R^(g2), R^(h2), and R^(i2) are the same or different, each independently

1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₁₀ alicyclic group, 4) C₆₋₁₀ aryl, 5) 5- or 6-membered heteroaryl, or 6) a 4- to 10-membered non-aryl heterocycle, (wherein each substituent from 2) to 6) is optionally substituted), and

a combination of R^(e2) and R^(f2), when attached to the same nitrogen atom, together may form an optionally substituted 4- to 10-membered nitrogen-containing non-aryl heterocycle.

R⁵ is C₆ aryl or 5-membered, 6-membered, 9-membered, or 10-membered heteroaryl selected from the group consisting of

d is the number of chemically substitutable positions on a ring of each group by R^(6a), and

each R^(6a) and each R^(6b) are defined the same as the present specification (e.g., item 46).

In some embodiments, R⁵ is C₆ aryl or 5-membered, 6-membered, 9-membered, or 10-membered heteroaryl selected from the group consisting of

d is the number of chemically substitutable positions on a ring of each group by R^(6a), and

each R^(6a) and each R^(6b) are defined the same as the definition herein (e.g., item 41).

In some embodiments, R^(6a), if there are multiple instances on the same ring, are all independently selected from the group consisting of

1) a hydrogen atom, 2) a hydroxyl group, 3) halogen, 4) a C₁₋₄ alkyl group (wherein the alkyl group is optionally substituted with NR^(e2)R^(f2), —C(═O)OR^(f2), —C(═O)NR^(e2)R^(f2), —C(═O)NR^(e2)(OR^(f2)), or a hydroxyl group), 5) a C₁₋₄ alkoxy group, 6) —NR^(e2)R^(f2), 7) —C(═O)NR^(e2)R^(f2), and

8) —C(═O)OR^(e2), and

each R^(6b), if there are multiple instances on the same ring, are all independently selected from the group consisting of 1) a hydrogen atom, 2) a hydroxyl group, and 3) a C₁₋₄ alkyl group

(wherein the alkyl group is optionally substituted with NR^(e2)R^(f2), —C(═O)OR^(f2), —C(═O)NR^(e2)R^(f2), —C(═O)NR^(e2)(OR^(f2)), or a hydroxyl group).

In some embodiments, R^(e2) and R^(f2) are the same or different, each independently a hydrogen atom, an optionally substituted C₁₋₆ alkyl group, or an optionally substituted C₃₋₁₀ alicyclic group. In some embodiments, R^(e2) and R^(f2) are the same or different, each independently a hydrogen atom or an optionally substituted C₁₋₆ alkyl group. In some embodiments, R^(e2) and R^(f2) are hydrogen atoms.

In some embodiments, R^(6a) is —NR^(e2)R^(f2), and one of R^(e2) and R^(f2) is a hydrogen atom and the other is a C₁₋₄ alkyl group (wherein the alkyl group is optionally substituted with an amino group or a hydroxyl group).

In some embodiments, R⁵ is C(═O)NR⁵⁰R⁵¹.

In some embodiments, R⁵⁰ represents

1) a hydrogen atom, 2) an optionally substituted C₁₋₄ alkyl group, 3) a hydroxyl group, 4) an optionally substituted C₁₋₄ alkoxy group, or 5) an optionally substituted C₁₋₆ alkylsulfonyl group,

R⁵¹ represents 1) a hydrogen atom or 2) an optionally substituted C₁₋₄ alkyl group, or

R⁵⁰ and R⁵¹ together may form a 4- to 6-membered nitrogen-containing non-aryl heterocycle.

In some embodiments, R⁵⁰ represents

1) a hydrogen atom, 2) a C₁₋₄ alkyl group (wherein the group is optionally substituted with halogen, a C₃₋₆ alicyclic group, —NR^(a21)R^(a22), or —OR^(c11)), 3) a hydroxyl group, 4) a C₁₋₄ alkoxy group (wherein the group is optionally substituted with halogen, a C₃₋₆ alicyclic group, —NR^(a23)R^(a24), or —OR^(c12)), or 5) a C₁₋₄ alkylsulfonyl group (wherein the group is optionally substituted with halogen, a C₃₋₆ alicyclic group, —NR^(a21)R^(a22), or —OR^(c11)),

R^(a21), R^(a22), R^(a23), R^(a24), R^(c11), and R^(c12) are the same or different, each independently representing 1) a hydrogen atom or 2) a C₁₋₄ alkyl group (wherein the group is optionally substituted with halogen),

wherein each combination of R^(a21) and R^(a22) or R^(a23) and R^(a24) together may form an optionally substituted 4- to 7-membered nitrogen-containing non-aryl heterocycle, and

R⁵¹ is a hydrogen atom or C₁₋₄ alkyl (wherein the group is optionally substituted with halogen).

In some embodiments, R⁵⁰ represents

1) a hydrogen atom, 2) a C₁₋₄ alkyl group (wherein the group is optionally substituted with a cyclopropyl group, —NH₂, —NHMe, —C(═O)NH₂, —C(═O)NHMe, —C(═O)NMe₂, or a -hydroxyl group), 3) a hydroxyl group, 4) a C₁₋₄ alkoxy group (wherein the group is optionally substituted with a cyclopropyl group, —NH₂, —NHMe, or a -hydroxyl group), or 5) a C₁₋₄ alkylsulfonyl group, and,

R⁵¹ is a hydrogen atom.

In some embodiments, R⁵⁰ represents

1) a hydrogen atom, 2) a C₁₋₄ alkyl group (wherein the group is optionally substituted with a cyclopropyl group, —NH₂, —NHMe, or a -hydroxyl group), 3) a hydroxyl group, 4) a C₁₋₄ alkoxy group (wherein the group is optionally substituted with a cyclopropyl group, —NH₂, —NHMe, or a -hydroxyl group), or 5) a C₁₋₄ alkylsulfonyl group, and

R⁵¹ is a hydrogen atom.

In some embodiments, R⁵ is —C(═O)OR²⁰

In some embodiments, R²⁰ is 1) a hydrogen atom or 2) an optionally substituted C₁₋₄ alkyl group.

In some embodiments, L³ is —CH₂—, and L⁴ is —CH(NH₂)— or —CMe(NH₂)—.

In some embodiments, L³ is —CH₂—, and

L⁴ is a single bond, —CH(NH₂)—, or —CMe(NH₂)—.

In some embodiments, L³ is —CH₂—, and L⁴ is

In some embodiments, L³ is —CH₂—, and L⁴ is

In some embodiments, R²⁰ is a hydrogen atom. In such a case, R⁵ is, specifically, —C(═O)OH (i.e., a carboxyl group).

In some embodiments, R⁵ is —NR^(e1)R^(f1),

L³ is —CH₂—,

L⁴ is —CR⁴⁰R⁴¹—, and

R⁴⁰ and R⁴¹ are each independently a C₁₋₄ alkyl group substituted with a hydroxyl group, or together with the carbon atom to which they are attached, form a C₃₋₆ alicyclic group.

In some embodiments, R⁵ is —NR^(e1), R^(f1), L³ is —CH₂—, L⁴ is —CR⁴⁰R⁴¹—, and R⁴⁰ and R⁴¹, together with the carbon atom to which they are attached, form a C₃₋₆ alicyclic group.

In some embodiments, R^(e1) and R^(f1) are the same or different, each independently

1) a hydrogen atom, or 2) an optionally substituted C₁₋₃ alkyl group, and

L⁴ is

In some embodiments, R^(e1) and R^(f1) are the same or different, each independently

1) a hydrogen atom, or 2) an optionally substituted C₁₋₃ alkyl group, and

L⁴ is a C₁₋₄ alkylene group substituted with a hydroxyl group.

In some embodiments, L⁴ is a single bond or a C₁₋₆ alkylene group optionally substituted with —NR²¹R²² or ═NOR²³, wherein R²¹, R²², and R²³ are each independently a hydrogen atom, an optionally substituted C₁₋₆ alkyl group, or an optionally substituted 4- to 10-membered non-aryl heterocyclyl carbonyl group.

In some embodiments, L⁴ is a single bond, —CH₂—, —CH(NH₂)—, —CMe(NH₂)—, —CH(NHMe)-, —CD(NH₂)— (wherein D represents a heavy hydrogen atom), —CH₂CH₂—, or —CH(NH₂)—CH₂—, wherein if an amino group is present in L⁴, carbon that attaches to the amino group attaches to L³.

In some embodiments, L³ is —C(═O)—, and

L⁴ is a single bond, —CH₂—, —CH(NH₂)—, —CMe(NH₂)—, or —CH(NH₂)—CH₂—.

In some embodiments, L³ is —C(═O)—, and L⁴ is —CH(NH₂)— or —CMe(NH₂)—.

In some embodiments, L⁴ is an isomeric structure of one of

In some embodiments, L³ is —C(═O)—, and L⁴ is an isomeric structure of one of

In some embodiments, L³ is —C(═O)—, and L⁴ is

In some embodiments, L⁴ is

In some embodiments, L⁴ is

In some embodiments, L⁴ is

In some embodiments, R⁵ is a hydrogen atom, an optionally substituted C₁₋₆ alkyl group, an optionally substituted C₃₋₁₀ alicyclic group, an optionally substituted 4- to 10-membered non-aryl heterocycle, optionally substituted C₆₋₁₀ aryl, optionally substituted 5- or 6-membered heteroaryl, an optionally substituted C₁₋₆ alkylthio group, or —NR^(e1)OH, wherein R^(e1) is a hydrogen atom or an optionally substituted C₁₋₆ alkyl group.

In some embodiments, R⁵ is a hydrogen atom, an optionally substituted C₁₋₆ alkyl group, an optionally substituted 4- to 10-membered non-aryl heterocycle, optionally substituted C₆₋₁₀ aryl, optionally substituted 5- or 6-membered heteroaryl, an optionally substituted C₁₋₆ alkylthio group, or —NR^(e1)OH, wherein R^(e1) is a hydrogen atom or an optionally substituted C₁₋₆ alkyl group.

In some embodiments, R⁵ is optionally substituted 5- or 6-membered heteroaryl or optionally substituted C₆₋₁₀ aryl.

In some embodiments, R⁵ is optionally substituted 5- or 6-membered heteroaryl.

In some embodiments, R⁵ is an optionally substituted C₄₋₁₀ alicyclic group or an optionally substituted 4- to 10-membered non-aryl heterocycle.

In some embodiments, R⁵ is an optionally substituted 4- to 10-membered non-aryl heterocycle.

In some embodiments, L⁴ is a single bond, and R⁵ is —NR^(e1)OH, wherein R^(e1) is a hydrogen atom or an optionally substituted C₁₋₆ alkyl group.

In some embodiments, L⁴ is

1) —(CH₂)_(p)—CR¹⁰(NHR¹¹)—, 2) —(CH₂)_(q)—CR¹²R¹³—, or 3) —(CH₂)_(p)—CR¹⁰(NHR¹¹)—(CH₂)_(q)—CR¹²R¹³— (wherein p and q are independently 0 or 1),

R¹⁰ is

1) a hydrogen atom, 2) a carboxyl group, or 3) —C(═O)NR^(10a)R^(10b),

R¹¹ is

1) a hydrogen atom,

2) —C(═O)R^(11a), or

3) an optionally substituted 5- or 6-membered non-aryl heterocyclyl carbonyl group, wherein if R¹⁰ is —C(═O)NR^(10a)R^(10b), R^(10b) and R¹¹ together may form —CH₂CH₂—,

R¹² is

1) a hydrogen atom, or 2) an optionally substituted C₁₋₄ alkyl group,

R¹³ is

1) a hydrogen atom, 2) a hydroxyl group, 3) an optionally substituted C₁₋₄ alkyl group, 4) a sulfanyl group, 5) a carboxyl group, 6) an optionally substituted C₁₋₄ alkylthio group, 7) —NR^(13a)R^(13b), 8) —NR^(13a)—C(═O)R^(13b), 9) an optionally substituted 5- or 6-membered non-aryl heterocyclyl carbonylamino group, 10) —NR^(13a)—C(═O)NR^(13b)R^(13c), 11) —C(═O)NR^(13a)R^(13b), 12) —C(═O)NR^(13a)OR^(13b), 13) —S(═O)₂—R^(13a), 14) —S(═O)₂—NR^(13a)R^(13b), 15) —C(═O)NR^(13a)—S(═O)₂—R^(13b), or 16) —C(═O)NR^(13a)—S(═O)₂—NR^(13b)R^(13c), and

R^(10a), R^(10b), R^(11a), R^(13a), R^(13b), and R^(13c) are each independently a hydrogen atom or an optionally substituted C₁₋₄ alkyl group. In such a case, in some embodiments, R⁵ is a hydrogen atom or an optionally substituted C₁₋₄ alkyl group.

In some embodiments, R⁵ is selected from the group consisting of

subscript d is the number of substitutable positions on a ring of R⁵,

each R^(6a) is independently selected from the group consisting of

1) a hydrogen atom, 2) a hydroxyl group, 3) a cyano group, 4) a nitro group, 5) halogen, 6) a C₁₋₄ alkyl group, 7) a C₃₋₁₀ alicyclic group, 8) a C₁₋₄ alkoxy group, 9) a C₃₋₁₀ alicyclic oxy group, 10) a C₆₋₁₀ aryloxy group, 11) a 5- or 6-membered heteroaryloxy group, 12) a 4- to 10-membered non-aryl heterocyclyl oxy group, (wherein each substituent from 6) to 12) is optionally substituted), 13) —SO₂—NR^(e2)R^(f2), 14) —NR^(g2)—CR^(e2)(═NR^(f2)), 15) —NR^(g2)—CR^(e2)(═N—OR^(f2)), 16) —NR^(h2)—C(═NR^(g2))NR^(e2)R^(f2), 17) —NR^(h2)—C(═N—OR^(g2))NR^(e2)R^(f2), 18) —NR^(i2)—C(═NR^(h2))NR^(g2)—NR^(e2)R^(f2), 19) —NR^(i2)—C(═N—OR^(h2))NR^(g2)—NR^(e2)R^(f2), 20) —C(═NR^(e2))R^(f2), 21) —C(═N—OR^(e2))R^(f2), 22) —C(═NR^(h2))—NR^(e2)R^(f2), 23) —C(═NR^(h2))NR^(g2)—NR^(e2)R^(f2), 24) —C(═N—OR^(h2))NR^(g2)—NR^(e2)R^(f2), 25) —NR^(e2)R^(f2), 26) —NR^(g2)—NR^(e2)R^(f2), 27) —NR^(e2)OR^(f2), 28) —NR^(e2)—C(═O)R^(f2), 29) —C(═O)NR^(e2)R^(f2), 30) —C(═O)NR^(e2)OR^(f2), 31) —C(═O)NR^(g2)—NR^(e2)R^(f2),

32) —C(═O)R^(e2), 33) —C(═O)OR^(e2), and

34) —C(═N—OR^(h2))NR^(e2)R^(f2), and

each R^(6b) is selected from the group consisting of

1) a hydrogen atom, 2) a hydroxyl group, 3) a C₁₋₄ alkyl group (wherein the alkyl group is optionally substituted), 4) a C₃₋₁₀ alicyclic group (wherein the alicyclic group is optionally substituted), 5) —C(═NR^(e2))R^(f2), 6) —C(═N—OR^(e2))R^(f2), 7) —SO₂—NR^(e2)R^(f2), 8) —C(═NR^(h2))—NR^(e2)R^(f2), 9) —C(═NR^(h2))NR^(g2)—NR^(e2)R^(f2), 10) —C(═N—OR^(h2))NR^(g2)—NR^(e2)R^(f2), 11) —C(═O)NR^(e2)R^(f2), 12) —C(═O)NR^(e2)OR^(f2), 13) —C(═O)NR^(g2)—NR^(e2)R^(f2),

14) —C(═O)R^(e2), and

15) —C(═N—OR^(h2))NR^(e2)R^(f2).

In some embodiments, R⁵ is 5- or 6-membered aryl or heteroaryl selected from the group consisting of

subscript d is the number of substitutable positions on a ring of R⁵,

each R^(6a) is independently selected from the group consisting of

1) a hydrogen atom, 2) a hydroxyl group, 3) halogen, 4) a C₁₋₄ alkyl group (wherein the alkyl group is optionally substituted with NR^(e2)R^(f2), a 5- or 6-membered non-aryl heterocycle, —C(═O)OR^(f2), or a hydroxyl group), 5) a C₁₋₄ alkoxy group, 6) —NR^(e2)R^(f2), and

7) —C(═O)OR^(e2), and

each R^(6b) is independently selected from the group consisting of

1) a hydrogen atom, 2) a hydroxyl group, and 3) a C₁₋₄ alkyl group (wherein the alkyl group is optionally substituted with NR^(e2)R^(f2), —C(═O)NR^(e2)R^(f2), —C(═O)OR^(f2), or a hydroxyl group).

In some embodiments, R⁵ is selected from the group consisting of

subscript d is the number of substitutable positions on a ring of R⁵,

each R^(6a) is independently selected from the group consisting of

1) a hydrogen atom, 2) a hydroxyl group, 3) a cyano group, 4) a nitro group, 5) halogen, 6) a C₁₋₄ alkyl group, 7) a C₃₋₁₀ alicyclic group, 8) a C₁₋₄ alkoxy group, 9) a C₃₋₁₀ alicyclic oxy group, 10) a C₆₋₁₀ aryloxy group, 11) a 5- or 6-membered heteroaryloxy group, 12) a 4- to 10-membered non-aryl heterocyclyl oxy group, (wherein each substituent from 6) to 12) is optionally substituted), 13) —SO₂—NR^(e2)R^(f2), 14) —NR^(g2)—CR^(e2)(═NR^(f2)), 15) —NR^(g2)—CR^(e2)(═N—OR^(f2)), 16) —NR^(h2)—C(═NR^(g2))NR^(e2)R^(f2), 17) —NR^(h2)—C(═N—OR^(g2))NR^(e2)R^(f2), 18) —NR^(i2)—C(═NR^(h2))NR^(g2)—NR^(e2)R^(f2), 19) —NR^(i2)—C(═N—OR^(h2))NR^(g2)—NR^(e2)R^(f2), 20) —C(═NR^(e2))R^(f2), 21) —C(═N—OR^(e2))R^(f2), 22) —C(═NR^(h2))—NR^(e2)R^(f2), 23) —C(═NR^(h2))NR^(g2)—NR^(e2)R^(f2), 24) —C(═N—OR^(h2))NR^(g2)—NR^(e2)R^(f2), 25) —NR^(e2)R^(f2), 26) —NR^(g2)—NR^(e2)R^(f2), 27) —NR^(e2)OR^(f2), 28) —NR^(e2)—C(═O)R^(f2), 29) —C(═O)NR^(e2)R^(f2), 30) —C(═O)NR^(e2)OR^(f2), 31) —C(═O)NR^(g2)—NR^(e2)R^(f2),

32) —C(═O)R^(e2), 33) —C(═O)OR^(e2), and

34) —C(═N—OR^(h2))NR^(e2)R^(f2), and

each R^(6b) is independently selected from the group consisting of

1) a hydrogen atom, 2) a hydroxyl group, 3) a C₁₋₄ alkyl group (wherein the alkyl group is optionally substituted), 4) a C₃₋₁₀ alicyclic group (wherein the alicyclic group is optionally substituted), 5) —C(═NR^(e2))R^(f2), 6) —C(═N—OR^(e2))R^(f2), 7) —SO₂—NR^(e2)R^(f2), 8) —C(═NR^(h2))—NR^(e2)R^(f2), 9) —C(═NR^(h2))NR^(g2)—NR^(e2)R^(f2), 10) —C(═N—OR^(h2))NR^(g2)—NR^(e2)R^(f2), 11) —C(═O)NR^(e2)R^(f2), 12) —C(═O)NR^(e2)OR^(f2), 13) —C(═O)NR^(g2)—NR^(e2)R^(f2),

14) —C(═O)R^(e2), and

15) —C(═N—OR^(h2))NR^(e2)R^(f2).

In some embodiments, R⁵ is 5- or 6-membered aryl or heteroaryl selected from the group consisting of

subscript d is the number of substitutable positions on a ring of R⁵,

each R^(6a) is independently selected from the group consisting of 1) a hydrogen atom, 2) a hydroxyl group, 3) halogen, 4) a C₁₋₄ alkyl group (wherein the alkyl group is optionally substituted with NR^(e2)R^(f2), a 5- or 6-membered non-aryl heterocycle, —C(═O)OR^(f2), or a hydroxyl group), 5) a C₁₋₄ alkoxy group, 6) —NR^(e2)R^(f2), and

7) —C(═O)OR^(e2), and

each R^(6b) is independently selected from the group consisting of

1) a hydrogen atom, 2) a hydroxyl group, and 3) a C₁₋₄ alkyl group (wherein the alkyl group is optionally substituted with NR^(e2)R^(f2), —C(═O)NR^(e2)R^(f2), —C(═O)OR^(f2), or a hydroxyl group).

In some embodiments, R⁵ is

In some embodiments, R^(e2) and R^(f2) are the same or different, each independently a hydrogen atom, an optionally substituted C₁₋₆ alkyl group, or an optionally substituted C₃₋₁₀ alicyclic group. In some embodiments, R^(e2) and R^(f2) are the same or different, each independently a hydrogen atom or an optionally substituted C₁₋₆ alkyl group. In some embodiments, R^(e2) and R^(f2) are hydrogen atoms.

In some embodiments, R⁶ is —NR^(e2)R^(f2), and one of R^(e2) and R^(f2) is a hydrogen atom and the other is a C₁₋₄ alkyl group (wherein the alkyl group is optionally substituted with an amino group or a hydroxyl group).

In some embodiments, R⁵ is a 4- to 6-membered non-aryl heterocycle selected from the group consisting of

subscript d is the number of substitutable positions on a ring of R⁵,

each R^(7a) is independently selected from the group consisting of

1) a hydrogen atom, 2) a hydroxyl group, 3) a cyano group, 4) halogen, 5) a C₁₋₄ alkyl group, 6) a C₃₋₁₀ alicyclic group, 7) a C₁₋₄ alkoxy group, 8) a C₃₋₁₀ alicyclic oxy group, 9) a C₆₋₁₀ aryloxy group, 10) a 5- or 6-membered heteroaryloxy group, 11) a 4- to 10-membered non-aryl heterocyclyl oxy group, (wherein each substituent from 5) and 11) is optionally substituted), 12) —SO₂—NR^(e3)R^(f3), 13) —NR^(g2)—CR^(e3)(═NR^(f3)), 14) —NR^(g2)—CR^(e3)(═N—OR^(f3)), 15) —NR^(h2)—C(═NR^(g2))NR^(e3)R^(f3), 16) —NR^(h2)—C(═N—OR^(g2))NR^(e3)R^(f3), 17) —NR^(i2)—C(═NR^(h2))NR^(g2)—NR^(e3)R^(f3), 18) —NR^(i2)—C(═N—OR^(h2))NR^(g2)—NR^(e3)R^(f3), 19) —C(═NR^(e3))R^(f3), 20) —C(═N—OR^(e3))R^(f3), 21) —C(═NR^(h2))—NR^(e3)R^(f3), 22) —C(═NR^(h2))NR^(g2)—NR^(e3)R^(f3), 23) —C(═N—OR^(h2))NR^(g2)—NR^(e3)R^(f3), 24) —NR^(e3)R^(f3), 25) —NR^(g2)—NR^(e3)R^(f3), 26) —NR^(e3)OR^(f3), 27) —NR^(e3)—C(═O)R^(f3), 28) —C(═O)NR^(e3)R^(f3), 29) —C(═O)NR^(e3)OR^(f3), 30) —C(═O)NR^(g2)—NR^(e3)R^(f3),

31) —C(═O)R^(e3), 32) —C(═O)OR^(e3), and

33) —C(═N—OR^(h2))NR^(e3)R^(f3),

each R^(7b) is independently selected from the group consisting of

1) a hydrogen atom, 2) a hydroxyl group, 3) a C₁₋₄ alkyl group (wherein the alkyl group is optionally substituted), 4) a C₃₋₁₀ alicyclic group (wherein the alicyclic group is optionally substituted), 5) —C(═NR^(e3))R^(f3), 6) —C(═N—OR^(e3))R^(f3), 7) —SO₂—NR^(e3)R^(f3), 8) —(═NR^(h2))—NR^(e3)R^(f3), 9) —C(═NR^(h2))—NR^(g2)—R^(e3)R^(f3), 10) —C(═N—OR^(h2))NR^(g2)—NR^(e3)R^(f3), 11) —C(═O)NR^(e3)R^(f3), 12) —C(═O)NR^(e3)OR^(f3), 13) —C(═O)NR^(g2)—NR^(e3)R^(f3),

14) —C(═O)R^(e3), and

15) —C(═N—OR^(h2))NR^(e3)R^(f3), and

R^(e3), R^(f3), R^(g2), R^(h2), and R^(i2) are defined the same as R^(e2), R^(f2), R^(g2), R^(h2), and R^(i2) defined herein.

In some embodiments, R⁵ is a 4- to 6-membered non-aryl heterocycle selected from the group consisting of

subscript d is the number of substitutable positions on a ring of R⁵,

each R^(7a) is independently selected from the group consisting of 1) a hydrogen atom, 2) a hydroxyl group, 3) halogen, 4) a C₁₋₄ alkyl group (wherein the alkyl group is optionally substituted with NR^(e3)R^(f3), a 5- or 6-membered non-aryl heterocycle, —C(═O)OR^(f3), or a hydroxyl group), 5) a C₁₋₄ alkoxy group, 6) —NR^(e3)R^(f3),

7) —C(═O)OR^(e3),

8) C₆₋₁₀ aryl, and 9) —C(═O)NR^(e3)R^(f3),

each R^(7b) is independently selected from the group consisting of

1) a hydrogen atom, 2) a hydroxyl group, and 3) a C₁₋₄ alkyl group (wherein the alkyl group is optionally substituted with NR^(e3)R^(f3), —C(═O)OR^(f3), or a hydroxyl group), and

R^(e3) and R^(f3) are defined the same as R^(e2) and R^(f2) described herein (e.g., any one of items 84 to 86).

In some embodiments, R⁵ is a 4- to 6-membered non-aryl heterocycle selected from the group consisting of

subscript d is the number of substitutable positions on a ring of R⁵,

each R^(7a) is independently selected from the group consisting of 1) a hydrogen atom, 2) a hydroxyl group, 3) halogen, 4) a C₁₋₄ alkyl group (wherein the alkyl group is optionally substituted with NR^(e3)R^(f3), a 5- or 6-membered non-aryl heterocycle, —C(═O)OR^(f3), or a hydroxyl group), 5) a C₁₋₄ alkoxy group, 6) —NR^(e3)R^(f3),

7) —C(═O)OR^(e3),

8) C₆₋₁₀ aryl, and 9) —C(═O)NR^(e3)R^(f3),

each R^(7b) is independently selected from the group consisting of

1) a hydrogen atom, 2) a hydroxyl group, and 3) a C₁₋₄ alkyl group (wherein the alkyl group is optionally substituted with NR^(e3)R^(f3), —C(═O)OR³, or a hydroxyl group), and

R^(e3) and R^(f3) are defined the same as R^(e2) and R^(f2) defined herein.

In some embodiments, R⁵ is C₄₋₆ cycloalkyl selected from the group consisting of

subscript d is the number of substitutable positions on a ring of R⁵,

each R⁹ is independently selected from the group consisting of

1) a hydrogen atom, 2) a hydroxyl group, 3) a cyano group, 4) halogen, 5) a C₁₋₄ alkyl group, 6) a C₃₋₁₀ alicyclic group, 7) a C₁₋₄ alkoxy group, 8) a C₃₋₁₀ alicyclic oxy group, 9) a C₆₋₁₀ aryloxy group, 10) a 5- or 6-membered heteroaryloxy group, 11) a 4- to 10-membered non-aryl heterocyclyl oxy group, (wherein each substituent from 5) and 11) is optionally substituted), 12) —SO₂—NR^(e3)R^(f3), 13) —NR^(g2)—CR^(e3)(═NR^(f3)), 14) —NR^(g2)—CR^(e3)(═N—OR^(f3)) 15) —NR^(h2)—C(═NR^(g2))NR^(e3)R^(f3), 16) —NR^(h2)—C(═N—OR^(g2))NR^(e3)R^(f3), 17) —NR^(i2)—C(═NR^(h2))NR^(g2)—NR^(e3)R^(f3), 18) —NR^(i2)—C(═N—OR^(h2))NR^(g2)—NR^(e3)R^(f3), 19) —C(═NR^(e3))R^(f3), 20) —C(═N—OR^(e3))R^(f3), 21) —C(═NR^(h2))—NR^(e3)R^(f3), 22) —C(═NR^(h2))NR^(g2)—NR^(e3)R^(f3), 23) —C(═N—OR^(h2))NR^(g2)—NR^(e3)R^(f3), 24) —NR^(e3)R^(f3), 25) —NR^(g2)—NR^(e3)R^(f3), 26) —NR^(e3)OR^(f3), 27) —NR^(e3)—C(═O)R^(f3), 28) —C(═O)NR^(e3)R^(f3), 29) —C(═O)NR^(e3)OR^(f3), 30) —C(═O)NR^(g2)—NR^(e3)R^(f3),

31) —C(═O)R^(e3), 32) —C(═O)OR^(e3), and

33) —C(═N—OR²)NR^(e3)R^(f3), and

R^(e3), R^(f3), R^(g2), R^(h2), and R^(i2) are defined the same as R^(e2) and R^(f2) described herein (e.g., item 3).

In some embodiments, R⁵ is C₄₋₆ cycloalkyl selected from the group consisting of

subscript d is the number of substitutable positions on a ring of R⁵,

each R⁹ is independently selected from the group consisting of

1) a hydrogen atom, 2) a hydroxyl group, 3) halogen, 4) a C₁₋₄ alkyl group (wherein the alkyl group is optionally substituted with NR^(e3)R^(f3), a 5- or 6-membered non-aryl heterocycle, —C(═O)OR^(f3), or a hydroxyl group), 5) a C₁₋₄ alkoxy group, 6) —NR^(e3)R^(f3),

7) —C(═O)OR^(e3),

8) C₆₋₁₀ aryl, and 9) —C(═O)NR^(e3)R^(f3), and

R^(e3) and R^(f3) are defined the same as R^(e2) and R^(f2) described herein (e.g., any of items 75 to 77).

In some embodiments, L⁴ is —CH(NH₂)—CHR¹³—, wherein carbon that attaches to the NH₂ attaches to L³,

R⁵ is a hydrogen atom, and

R¹³ is

1) —NH—C(═O) CH₃, 2) —NH—C(═O)NH₂,

3) —NH—C(═O)CH(NH₂)—CH₂C(═O)NH₂, 4) —NH—C(═O) CH₂—NH₂, 5) —NH—C(═O)CH(NH₂)—CH₂OH, or 6) a pyrrolidin-2-ylcarbonylamino group.

In some embodiments, L⁴ is —CH(NH₂)—CR¹²R¹³—, wherein carbon that attaches to the NH₂ attaches to L³,

R⁵ is a hydrogen atom or methyl,

R¹² is a hydrogen atom or methyl, and

R¹³ is a benzylthio group or a sulfanyl group.

In some embodiments, L⁴ is —CH(NH₂)—(CH₂)_(q)—CHR¹³—, wherein q is 0 or 1, and carbon that attaches to the NH₂ attaches to L³,

R⁵ is a hydrogen atom, and

R¹³ is

1) a carboxyl group,

2) —C(═O)NH₂, 3) —C(═O)NH(CH₃),

4) —C(═O)N(CH₃)₂, 5) —C(═O)NH—(CH₂)₂—OH, 6) —C(═O)NH—(CH₂)₂—NH₂, 7) —C(═O)NH—S(═O)₂—CH₃,

8) —C(═O)NHOH,

9) —S(═O)₂—NH₂, 10) —S(═O)₂—CH₃, or 11) a hydroxyl group.

In some embodiments, L⁴ is —CH(NHR¹¹)—CH₂—, wherein carbon that attaches to the NHR¹¹ attaches to L³,

R⁵ is hydrogen, and

R¹¹ is

1) —C(═O)CH(NH₂)—CH₂C(═O)NH₂, 2) —C(═O)CH₂—NH₂, 3) —C(═O)CH(CH₃)—NH₂, 4) —C(═O)CH(NH₂)—CH₂OH, or 5) pyrrolidin-2-ylcarbonyl.

In some embodiments, L⁴ is —CH(NHR¹¹)—CH(COOH)—, wherein carbon that attaches to the NHR¹¹ attaches to L³,

R⁵ is hydrogen, and

R¹¹ is

1) —C(═O)CH(NH₂)—CH₂C(═O)NH₂, 2) —C(═O)CH₂—NH₂, 3) —C(═O)CH(CH₃)—NH₂, 4) —C(═O)CH(NH₂)—CH₂OH, or 5) pyrrolidin-2-ylcarbonyl.

In some embodiments, L⁴ is —CHR¹³— or —CH₂—CHR¹³—,

R⁵ is hydrogen, and

R¹³ is —C(═O)NH₂ or —C(═O)NHOH.

In some embodiments, L⁴ is —CH₂—CR¹⁰(NH₂)—, wherein the CH₂ group attaches to L³,

R⁵ is hydrogen, and

R¹⁰ is a carboxy group or —C(═O)NH₂.

In some embodiments, L⁴ is —(CH₂)_(p)—CR¹⁰(NHR¹¹)—(CH₂)_(q)—CHR¹³— or —CHR¹³—(CH₂)_(q)—CR¹⁰(NHR¹¹)—(CH₂)_(p)—, wherein q is 0 or 1,

R⁵ is hydrogen,

(1) if L⁴ is —CHR³—(CH₂)_(q)—CR¹⁰(NHR¹¹)—(CH₂)_(p)—, carbon of the —CHR¹³— group attaches to L³,

p is 0,

R¹⁰ is a hydrogen atom, a carboxyl group, or —C(═O)NHR^(b),

R¹¹ is a hydrogen atom,

R^(10b) is a hydrogen atom,

wherein if R¹⁰ is —C(═O)NHR^(10b), R^(10b) and R¹¹ together may form —CH₂CH₂—, and

R¹³ is a hydrogen atom, and

(2) if L⁴ is —(CH₂)_(p)—CR¹⁰(NHR¹¹)—(CH₂)_(q)—CHR¹³—, carbon of the —(CH₂)_(p)— group attaches to L³,

p is 1,

R¹⁰ and R¹¹ are both hydrogen atoms,

R¹³ is a carboxyl group or —C(═O)NR^(13a)R^(13b), and

R^(13a) and R^(13b) are each independently a hydrogen atom or an optionally substituted C₁₋₄ alkyl group.

In some embodiments, L⁴ is —CR¹²(NH₂)—,

R¹² is a hydrogen atom or a methyl group, and

R⁵ is an optionally substituted C₁₋₄ alkyl group with a hydroxyl group.

A specific example of a specific embodiment of the compound of the invention includes compounds represented by formulas (3a) and (3b):

or a pharmaceutically acceptable salt thereof, wherein X, R¹, R², and R³ are as defined herein, and R⁴ is selected from the group consisting of 1) —C(═O)OR^(m1) (wherein R^(m1) is a hydrogen atom, a C₁₋₆ alkyl group, a C₃₋₁₀ alicyclic group, C₆₋₁₀ aryl, 5- or 6-membered heteroaryl, or a 4- to 10-membered non-aryl heterocycle, wherein the C₁₋₆ alkyl group, the C₃₋₁₀ alicyclic group, the C₆₋₁₀ aryl, the 5- or 6-membered heteroaryl, and the 4- to 10-membered non-aryl heterocycle are each optionally substituted), and 2) a bioisostere of 1).

A specific example of a preferred embodiment of the compound of the invention includes compounds represented by formulas (4a) and (4b):

or a pharmaceutically acceptable salt thereof. In formulas (4a) and (4b), X, R⁴, Y, ring A, L³, L⁴, and R³ are defined the same as the definitions herein, and R¹ and R² are the same or different, each independently a hydrogen atom, a halogen atom, a C₁₋₆ alkyl group, a C₁₋₆ alkoxy group, or a C₁₋₆ alkylthio group (wherein the C₁₋₆ alkyl group, C₁₋₆ alkoxy group, and C₁₋₆ alkylthio group are optionally substituted).

A specific example of a more preferred embodiment of the compound of the invention includes compounds represented by formulas (5a) and (5b):

or a pharmaceutically acceptable salt thereof. In formulas (5a) and (5b), R¹, R², Y, L³, L⁴, and R⁵ are defined the same as the definitions herein, and ring A is an optionally substituted 4- to 6-membered nitrogen-containing non-aryl heterocycle.

A specific example of a still more preferred embodiment of the compound of the invention includes compounds represented by formulas (6a) and (6b):

or a pharmaceutically acceptable salt thereof. In formulas (6a) and (6b), L³, L⁴, and R⁵ are defined the same as the definitions herein,

m is an integer 1, 2, or 3,

n is an integer 1, 2, or 3, and

m+n is 2, 3, or 4.

A specific example of a yet still more preferred embodiment of the compound of the invention includes enantiomers represented by formulas (7a) and (7b):

formulas (8a) and (8b):

or a pharmaceutically acceptable salt thereof. In formulas (7a), (7b), (8a), and (8b), L³, L⁴, R⁵, m, and n are defined the same as the definitions herein.

A specific example of a preferred embodiment of the compound of the invention includes the following compounds:

compounds represented by

or a pharmaceutically acceptable salt thereof, wherein

R^(ZL) is a substituent selected from the group consisting of the Z1 to Z4 described below,

one of R¹, R², and R³ is

and

the remaining two are hydrogen atoms, linking group L^(a) is a substituent selected from the group consisting of L1 to L69 described below, and substituent Q^(a) is a substituent selected from the group consisting of Q1 to Q161 described below;

R^(ZL):

linking group L^(a):

and substituent Q^(a):

A specific example of a more preferred embodiment of the compound of the invention includes a compound of the following formula:

or a pharmaceutically acceptable salt thereof, wherein R³ is

wherein linking group L^(a) is a substituent selected from the group consisting of L1 to L69 described above, and substituent Q^(a) is a substituent selected from the group consisting of Q1 to Q161 described above.

Examples of a more preferred embodiment of the compound of the invention include the compounds of the following Table (1) or a pharmaceutically acceptable salt thereof.

TABLE 1 Example L* Q* 1 L1 Q1 2 L1 Q2 3 L1 Q3 4 L1 Q4 5 L1 Q5 6 L1 Q6 7 L1 Q7 8 L1 Q8 9 L1 Q9 10 L1 Q10 11 L1 Q11 12 L1 Q12 13 L1 Q13 14 L1 Q14 15 L1 Q15 16 L1 Q16 17 L1 Q17 18 L1 Q18 19 L1 Q19 20 L1 Q20 21 L1 Q21 22 L1 Q22 23 L1 Q23 24 L1 Q24 25 L1 Q25 26 L1 Q26 27 L1 Q27 28 L1 Q28 29 L1 Q29 30 L1 Q30 31 L1 Q31 32 L1 Q32 33 L1 Q33 34 L1 Q34 35 L1 Q35 36 L1 Q36 37 L1 Q37 38 L1 Q38 39 L1 Q39 40 L1 Q40 41 L1 Q41 42 L1 Q42 43 L1 Q43 44 L1 Q44 45 L1 Q45 46 L1 Q46 47 L1 Q47 48 L1 Q48 49 L1 Q49 50 L1 Q50 51 L1 Q51 52 L1 Q52 53 L1 Q53 54 L1 Q54 55 L1 Q55 56 L1 Q56 57 L1 Q57 58 L1 Q58 59 L1 Q59 60 L1 Q60 61 L1 Q61 62 L1 Q62 63 L1 Q63 64 L1 Q64 65 L1 Q65 66 L1 Q66 67 L1 Q67 68 L1 Q68 69 L1 Q69 70 L1 Q70 71 L1 Q71 72 L1 Q72 73 L1 Q73 74 L1 Q74 75 L1 Q75 76 L1 Q76 77 L1 Q77 78 L1 Q78 79 L1 Q79 80 L1 Q80 81 L1 Q81 82 L1 Q82 83 L1 Q83 84 L1 Q84 85 L1 Q85 86 L1 Q86 87 L1 Q87 88 L1 Q88 89 L1 Q89 90 L1 Q90 91 L1 Q91 92 L1 Q92 93 L1 Q93 94 L1 Q94 95 L1 Q95 96 L1 Q96 97 L1 Q97 98 L1 Q98 99 L1 Q99 100 L1 Q100 101 L1 Q101 102 L1 Q102 103 L1 Q103 104 L1 Q104 105 L1 Q105 106 L1 Q106 107 L1 Q107 108 L1 Q108 109 L1 Q109 110 L1 Q110 111 L1 Q111 112 L1 Q112 113 L1 Q113 114 L1 Q114 115 L1 Q115 116 L1 Q116 117 L1 Q117 118 L1 Q118 119 L1 Q119 120 L1 Q120 121 L1 Q121 122 L1 Q122 123 L1 Q123 124 L1 Q124 125 L1 Q125 126 L1 Q126 127 L1 Q127 128 L1 Q128 129 L1 Q129 130 L1 Q130 131 L1 Q131 132 L1 Q132 133 L1 Q133 134 L1 Q134 135 L1 Q135 136 L1 Q136 137 L1 Q137 138 L1 Q138 139 L1 Q139 140 L1 Q140 141 L1 Q141 142 L1 Q142 143 L1 Q143 144 L1 Q144 145 L1 Q145 146 L1 Q146 147 L1 Q147 148 L1 Q148 149 L1 Q149 150 L1 Q150 151 L1 Q151 152 L1 Q152 153 L1 Q153 154 L1 Q154 155 L1 Q155 156 L1 Q156 157 L1 Q157 158 L1 Q158 159 L1 Q159 160 L1 Q160 161 L1 Q161 162 L2 Q1 163 L2 Q2 164 L2 Q3 165 L2 Q4 166 L2 Q5 167 L2 Q6 168 L2 Q7 169 L2 Q8 170 L2 Q9 171 L2 Q10 172 L2 Q11 173 L2 Q12 174 L2 Q13 175 L2 Q14 176 L2 Q15 177 L2 Q16 178 L2 Q17 179 L2 Q18 180 L2 Q19 181 L2 Q20 182 L2 Q21 183 L2 Q22 184 L2 Q23 185 L2 Q24 186 L2 Q25 187 L2 Q26 188 L2 Q27 189 L2 Q28 190 L2 Q29 191 L2 Q30 192 L2 Q31 193 L2 Q32 194 L2 Q33 195 L2 Q34 196 L2 Q35 197 L2 Q36 198 L2 Q37 199 L2 Q38 200 L2 Q39 201 L2 Q40 202 L2 Q41 203 L2 Q42 204 L2 Q43 205 L2 Q44 206 L2 Q45 207 L2 Q46 208 L2 Q47 209 L2 Q48 210 L2 Q49 211 L2 Q50 212 L2 Q51 213 L2 Q52 214 L2 Q53 215 L2 Q54 216 L2 Q55 217 L2 Q56 218 L2 Q57 219 L2 Q58 220 L2 Q59 221 L2 Q60 222 L2 Q61 223 L2 Q62 224 L2 Q63 225 L2 Q64 226 L2 Q65 227 L2 Q66 228 L2 Q67 229 L2 Q68 230 L2 Q69 231 L2 Q70 232 L2 Q71 233 L2 Q72 234 L2 Q73 235 L2 Q74 236 L2 Q75 237 L2 Q76 238 L2 Q77 239 L2 Q78 240 L2 Q79 241 L2 Q80 242 L2 Q81 243 L2 Q82 244 L2 Q83 245 L2 Q84 246 L2 Q85 247 L2 Q86 248 L2 Q87 249 L2 Q88 250 L2 Q89 251 L2 Q90 252 L2 Q91 253 L2 Q92 254 L2 Q93 255 L2 Q94 256 L2 Q95 257 L2 Q96 258 L2 Q97 259 L2 Q98 260 L2 Q99 261 L2 Q100 262 L2 Q101 263 L2 Q102 264 L2 Q103 265 L2 Q104 266 L2 Q105 267 L2 Q106 268 L2 Q107 269 L2 Q108 270 L2 Q109 271 L2 Q110 272 L2 Q111 273 L2 Q112 274 L2 Q113 275 L2 Q114 276 L2 Q115 277 L2 Q116 278 L2 Q117 279 L2 Q118 280 L2 Q119 281 L2 Q120 282 L2 Q121 283 L2 Q122 284 L2 Q123 285 L2 Q124 286 L2 Q125 287 L2 Q126 288 L2 Q127 289 L2 Q128 290 L2 Q129 291 L2 Q130 292 L2 Q131 293 L2 Q132 294 L2 Q133 295 L2 Q134 296 L2 Q135 297 L2 Q136 298 L2 Q137 299 L2 Q138 300 L2 Q139 301 L2 Q140 302 L2 Q141 303 L2 Q142 304 L2 Q143 305 L2 Q144 306 L2 Q145 307 L2 Q146 308 L2 Q147 309 L2 Q148 310 L2 Q149 311 L2 Q150 312 L2 Q151 313 L2 Q152 314 L2 Q153 315 L2 Q154 316 L2 Q155 317 L2 Q156 318 L2 Q157 319 L2 Q158 320 L2 Q159 321 L2 Q160 322 L2 Q161 323 L3 Q1 324 L3 Q2 325 L3 Q3 326 L3 Q4 327 L3 Q5 328 L3 Q6 329 L3 Q7 330 L3 Q8 331 L3 Q9 332 L3 Q10 333 L3 Q11 334 L3 Q12 335 L3 Q13 336 L3 Q14 337 L3 Q15 338 L3 Q16 339 L3 Q17 340 L3 Q18 341 L3 Q19 342 L3 Q20 343 L3 Q21 344 L3 Q22 345 L3 Q23 346 L3 Q24 347 L3 Q25 348 L3 Q26 349 L3 Q27 350 L3 Q28 351 L3 Q29 352 L3 Q30 353 L3 Q31 354 L3 Q32 355 L3 Q33 356 L3 Q34 357 L3 Q35 358 L3 Q36 359 L3 Q37 360 L3 Q38 361 L3 Q39 362 L3 Q40 363 L3 Q41 364 L3 Q42 365 L3 Q43 366 L3 Q44 367 L3 Q45 368 L3 Q46 369 L3 Q47 370 L3 Q48 371 L3 Q49 372 L3 Q50 373 L3 Q51 374 L3 Q52 375 L3 Q53 376 L3 Q54 377 L3 Q55 378 L3 Q56 379 L3 Q57 380 L3 Q58 381 L3 Q59 382 L3 Q60 383 L3 Q61 384 L3 Q62 385 L3 Q63 386 L3 Q64 387 L3 Q65 388 L3 Q66 389 L3 Q67 390 L3 Q68 391 L3 Q69 392 L3 Q70 393 L3 Q71 394 L3 Q72 395 L3 Q73 396 L3 Q74 397 L3 Q75 398 L3 Q76 399 L3 Q77 400 L3 Q78 401 L3 Q79 402 L3 Q80 403 L3 Q81 404 L3 Q82 405 L3 Q83 406 L3 Q84 407 L3 Q85 408 L3 Q86 409 L3 Q87 410 L3 Q88 411 L3 Q89 412 L3 Q90 413 L3 Q91 414 L3 Q92 415 L3 Q93 416 L3 Q94 417 L3 Q95 418 L3 Q96 419 L3 Q97 420 L3 Q98 421 L3 Q99 422 L3 Q100 423 L3 Q101 424 L3 Q102 425 L3 Q103 426 L3 Q104 427 L3 Q105 428 L3 Q106 429 L3 Q107 430 L3 Q108 431 L3 Q109 432 L3 Q110 433 L3 Q111 434 L3 Q112 435 L3 Q113 436 L3 Q114 437 L3 Q115 438 L3 Q116 439 L3 Q117 440 L3 Q118 441 L3 Q119 442 L3 Q120 443 L3 Q121 444 L3 Q122 445 L3 Q123 446 L3 Q124 447 L3 Q125 448 L3 Q126 449 L3 Q127 450 L3 Q128 451 L3 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L4 Q144 628 L4 Q145 629 L4 Q146 630 L4 Q147 631 L4 Q148 632 L4 Q149 633 L4 Q150 634 L4 Q151 635 L4 Q152 636 L4 Q153 637 L4 Q154 638 L4 Q155 639 L4 Q156 640 L4 Q157 641 L4 Q158 642 L4 Q159 643 L4 Q160 644 L4 Q161 645 L5 Q1 646 L5 Q2 647 L5 Q3 648 L5 Q4 649 L5 Q5 650 L5 Q6 651 L5 Q7 652 L5 Q8 653 L5 Q9 654 L5 Q10 655 L5 Q11 656 L5 Q12 657 L5 Q13 658 L5 Q14 659 L5 Q15 660 L5 Q16 661 L5 Q17 662 L5 Q18 663 L5 Q19 664 L5 Q20 665 L5 Q21 666 L5 Q22 667 L5 Q23 668 L5 Q24 669 L5 Q25 670 L5 Q26 671 L5 Q27 672 L5 Q28 673 L5 Q29 674 L5 Q30 675 L5 Q31 676 L5 Q32 677 L5 Q33 678 L5 Q34 679 L5 Q35 680 L5 Q36 681 L5 Q37 682 L5 Q38 683 L5 Q39 684 L5 Q40 685 L5 Q41 686 L5 Q42 687 L5 Q43 688 L5 Q44 689 L5 Q45 690 L5 Q46 691 L5 Q47 692 L5 Q48 693 L5 Q49 694 L5 Q50 695 L5 Q51 696 L5 Q52 697 L5 Q53 698 L5 Q54 699 L5 Q55 700 L5 Q56 701 L5 Q57 702 L5 Q58 703 L5 Q59 704 L5 Q60 705 L5 Q61 706 L5 Q62 707 L5 Q63 708 L5 Q64 709 L5 Q65 710 L5 Q66 711 L5 Q67 712 L5 Q68 713 L5 Q69 714 L5 Q70 715 L5 Q71 716 L5 Q72 717 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803 L5 Q159 804 L5 Q160 805 L5 Q161 806 L6 Q1 807 L6 Q2 808 L6 Q3 809 L6 Q4 810 L6 Q5 811 L6 Q6 812 L6 Q7 813 L6 Q8 814 L6 Q9 815 L6 Q10 816 L6 Q11 817 L6 Q12 818 L6 Q13 819 L6 Q14 820 L6 Q15 821 L6 Q16 822 L6 Q17 823 L6 Q18 824 L6 Q19 825 L6 Q20 826 L6 Q21 827 L6 Q22 828 L6 Q23 829 L6 Q24 830 L6 Q25 831 L6 Q26 832 L6 Q27 833 L6 Q28 834 L6 Q29 835 L6 Q30 836 L6 Q31 837 L6 Q32 838 L6 Q33 839 L6 Q34 840 L6 Q35 841 L6 Q36 842 L6 Q37 843 L6 Q38 844 L6 Q39 845 L6 Q40 846 L6 Q41 847 L6 Q42 848 L6 Q43 849 L6 Q44 850 L6 Q45 851 L6 Q46 852 L6 Q47 853 L6 Q48 854 L6 Q49 855 L6 Q50 856 L6 Q51 857 L6 Q52 858 L6 Q53 859 L6 Q54 860 L6 Q55 861 L6 Q56 862 L6 Q57 863 L6 Q58 864 L6 Q59 865 L6 Q60 866 L6 Q61 867 L6 Q62 868 L6 Q63 869 L6 Q64 870 L6 Q65 871 L6 Q66 872 L6 Q67 873 L6 Q68 874 L6 Q69 875 L6 Q70 876 L6 Q71 877 L6 Q72 878 L6 Q73 879 L6 Q74 880 L6 Q75 881 L6 Q76 882 L6 Q77 883 L6 Q78 884 L6 Q79 885 L6 Q80 886 L6 Q81 887 L6 Q82 888 L6 Q83 889 L6 Q84 890 L6 Q85 891 L6 Q86 892 L6 Q87 893 L6 Q88 894 L6 Q89 895 L6 Q90 896 L6 Q91 897 L6 Q92 898 L6 Q93 899 L6 Q94 900 L6 Q95 901 L6 Q96 902 L6 Q97 903 L6 Q98 904 L6 Q99 905 L6 Q100 906 L6 Q101 907 L6 Q102 908 L6 Q103 909 L6 Q104 910 L6 Q105 911 L6 Q106 912 L6 Q107 913 L6 Q108 914 L6 Q109 915 L6 Q110 916 L6 Q111 917 L6 Q112 918 L6 Q113 919 L6 Q114 920 L6 Q115 921 L6 Q116 922 L6 Q117 923 L6 Q118 924 L6 Q119 925 L6 Q120 926 L6 Q121 927 L6 Q122 928 L6 Q123 929 L6 Q124 930 L6 Q125 931 L6 Q126 932 L6 Q127 933 L6 Q128 934 L6 Q129 935 L6 Q130 936 L6 Q131 937 L6 Q132 938 L6 Q133 939 L6 Q134 940 L6 Q135 941 L6 Q136 942 L6 Q137 943 L6 Q138 944 L6 Q139 945 L6 Q140 946 L6 Q141 947 L6 Q142 948 L6 Q143 949 L6 Q144 950 L6 Q145 951 L6 Q146 952 L6 Q147 953 L6 Q148 954 L6 Q149 955 L6 Q150 956 L6 Q151 957 L6 Q152 958 L6 Q153 959 L6 Q154 960 L6 Q155 961 L6 Q156 962 L6 Q157 963 L6 Q158 964 L6 Q159 965 L6 Q160 966 L6 Q161 967 L7 Q1 968 L7 Q2 969 L7 Q3 970 L7 Q4 971 L7 Q5 972 L7 Q6 973 L7 Q7 974 L7 Q8 975 L7 Q9 976 L7 Q10 977 L7 Q11 978 L7 Q12 979 L7 Q13 980 L7 Q14 981 L7 Q15 982 L7 Q16 983 L7 Q17 984 L7 Q18 985 L7 Q19 986 L7 Q20 987 L7 Q21 988 L7 Q22 989 L7 Q23 990 L7 Q24 991 L7 Q25 992 L7 Q26 993 L7 Q27 994 L7 Q28 995 L7 Q29 996 L7 Q30 997 L7 Q31 998 L7 Q32 999 L7 Q33 1000 L7 Q34 1001 L7 Q35 1002 L7 Q36 1003 L7 Q37 1004 L7 Q38 1005 L7 Q39 1006 L7 Q40 1007 L7 Q41 1008 L7 Q42 1009 L7 Q43 1010 L7 Q44 1011 L7 Q45 1012 L7 Q46 1013 L7 Q47 1014 L7 Q48 1015 L7 Q49 1016 L7 Q50 1017 L7 Q51 1018 L7 Q52 1019 L7 Q53 1020 L7 Q54 1021 L7 Q55 1022 L7 Q56 1023 L7 Q57 1024 L7 Q58 1025 L7 Q59 1026 L7 Q60 1027 L7 Q61 1028 L7 Q62 1029 L7 Q63 1030 L7 Q64 1031 L7 Q65 1032 L7 Q66 1033 L7 Q67 1034 L7 Q68 1035 L7 Q69 1036 L7 Q70 1037 L7 Q71 1038 L7 Q72 1039 L7 Q73 1040 L7 Q74 1041 L7 Q75 1042 L7 Q76 1043 L7 Q77 1044 L7 Q78 1045 L7 Q79 1046 L7 Q80 1047 L7 Q81 1048 L7 Q82 1049 L7 Q83 1050 L7 Q84 1051 L7 Q85 1052 L7 Q86 1053 L7 Q87 1054 L7 Q88 1055 L7 Q89 1056 L7 Q90 1057 L7 Q91 1058 L7 Q92 1059 L7 Q93 1060 L7 Q94 1061 L7 Q95 1062 L7 Q96 1063 L7 Q97 1064 L7 Q98 1065 L7 Q99 1066 L7 Q100 1067 L7 Q101 1068 L7 Q102 1069 L7 Q103 1070 L7 Q104 1071 L7 Q105 1072 L7 Q106 1073 L7 Q107 1074 L7 Q108 1075 L7 Q109 1076 L7 Q110 1077 L7 Q111 1078 L7 Q112 1079 L7 Q113 1080 L7 Q114 1081 L7 Q115 1082 L7 Q116 1083 L7 Q117 1084 L7 Q118 1085 L7 Q119 1086 L7 Q120 1087 L7 Q121 1088 L7 Q122 1089 L7 Q123 1090 L7 Q124 1091 L7 Q125 1092 L7 Q126 1093 L7 Q127 1094 L7 Q128 1095 L7 Q129 1096 L7 Q130 1097 L7 Q131 1098 L7 Q132 1099 L7 Q133 1100 L7 Q134 1101 L7 Q135 1102 L7 Q136 1103 L7 Q137 1104 L7 Q138 1105 L7 Q139 1106 L7 Q140 1107 L7 Q141 1108 L7 Q142 1109 L7 Q143 1110 L7 Q144 1111 L7 Q145 1112 L7 Q146 1113 L7 Q147 1114 L7 Q148 1115 L7 Q149 1116 L7 Q150 1117 L7 Q151 1118 L7 Q152 1119 L7 Q153 1120 L7 Q154 1121 L7 Q155 1122 L7 Q156 1123 L7 Q157 1124 L7 Q158 1125 L7 Q159 1126 L7 Q160 1127 L7 Q161 1128 L8 Q1 1129 L8 Q2 1130 L8 Q3 1131 L8 Q4 1132 L8 Q5 1133 L8 Q6 1134 L8 Q7 1135 L8 Q8 1136 L8 Q9 1137 L8 Q10 1138 L8 Q11 1139 L8 Q12 1140 L8 Q13 1141 L8 Q14 1142 L8 Q15 1143 L8 Q16 1144 L8 Q17 1145 L8 Q18 1146 L8 Q19 1147 L8 Q20 1148 L8 Q21 1149 L8 Q22 1150 L8 Q23 1151 L8 Q24 1152 L8 Q25 1153 L8 Q26 1154 L8 Q27 1155 L8 Q28 1156 L8 Q29 1157 L8 Q30 1158 L8 Q31 1159 L8 Q32 1160 L8 Q33 1161 L8 Q34 1162 L8 Q35 1163 L8 Q36 1164 L8 Q37 1165 L8 Q38 1166 L8 Q39 1167 L8 Q40 1168 L8 Q41 1169 L8 Q42 1170 L8 Q43 1171 L8 Q44 1172 L8 Q45 1173 L8 Q46 1174 L8 Q47 1175 L8 Q48 1176 L8 Q49 1177 L8 Q50 1178 L8 Q51 1179 L8 Q52 1180 L8 Q53 1181 L8 Q54 1182 L8 Q55 1183 L8 Q56 1184 L8 Q57 1185 L8 Q58 1186 L8 Q59 1187 L8 Q60 1188 L8 Q61 1189 L8 Q62 1190 L8 Q63 1191 L8 Q64 1192 L8 Q65 1193 L8 Q66 1194 L8 Q67 1195 L8 Q68 1196 L8 Q69 1197 L8 Q70 1198 L8 Q71 1199 L8 Q72 1200 L8 Q73 1201 L8 Q74 1202 L8 Q75 1203 L8 Q76 1204 L8 Q77 1205 L8 Q78 1206 L8 Q79 1207 L8 Q80 1208 L8 Q81 1209 L8 Q82 1210 L8 Q83 1211 L8 Q84 1212 L8 Q85 1213 L8 Q86 1214 L8 Q87 1215 L8 Q88 1216 L8 Q89 1217 L8 Q90 1218 L8 Q91 1219 L8 Q92 1220 L8 Q93 1221 L8 Q94 1222 L8 Q95 1223 L8 Q96 1224 L8 Q97 1225 L8 Q98 1226 L8 Q99 1227 L8 Q100 1228 L8 Q101 1229 L8 Q102 1230 L8 Q103 1231 L8 Q104 1232 L8 Q105 1233 L8 Q106 1234 L8 Q107 1235 L8 Q108 1236 L8 Q109 1237 L8 Q110 1238 L8 Q111 1239 L8 Q112 1240 L8 Q113 1241 L8 Q114 1242 L8 Q115 1243 L8 Q116 1244 L8 Q117 1245 L8 Q118 1246 L8 Q119 1247 L8 Q120 1248 L8 Q121 1249 L8 Q122 1250 L8 Q123 1251 L8 Q124 1252 L8 Q125 1253 L8 Q126 1254 L8 Q127 1255 L8 Q128 1256 L8 Q129 1257 L8 Q130 1258 L8 Q131 1259 L8 Q132 1260 L8 Q133 1261 L8 Q134 1262 L8 Q135 1263 L8 Q136 1264 L8 Q137 1265 L8 Q138 1266 L8 Q139 1267 L8 Q140 1268 L8 Q141 1269 L8 Q142 1270 L8 Q143 1271 L8 Q144 1272 L8 Q145 1273 L8 Q146 1274 L8 Q147 1275 L8 Q148 1276 L8 Q149 1277 L8 Q150 1278 L8 Q151 1279 L8 Q152 1280 L8 Q153 1281 L8 Q154 1282 L8 Q155 1283 L8 Q156 1284 L8 Q157 1285 L8 Q158 1286 L8 Q159 1287 L8 Q160 1288 L8 Q161 1289 L9 Q1 1290 L9 Q2 1291 L9 Q3 1292 L9 Q4 1293 L9 Q5 1294 L9 Q6 1295 L9 Q7 1296 L9 Q8 1297 L9 Q9 1298 L9 Q10 1299 L9 Q11 1300 L9 Q12 1301 L9 Q13 1302 L9 Q14 1303 L9 Q15 1304 L9 Q16 1305 L9 Q17 1306 L9 Q18 1307 L9 Q19 1308 L9 Q20 1309 L9 Q21 1310 L9 Q22 1311 L9 Q23 1312 L9 Q24 1313 L9 Q25 1314 L9 Q26 1315 L9 Q27 1316 L9 Q28 1317 L9 Q29 1318 L9 Q30 1319 L9 Q31 1320 L9 Q32 1321 L9 Q33 1322 L9 Q34 1323 L9 Q35 1324 L9 Q36 1325 L9 Q37 1326 L9 Q38 1327 L9 Q39 1328 L9 Q40 1329 L9 Q41 1330 L9 Q42 1331 L9 Q43 1332 L9 Q44 1333 L9 Q45 1334 L9 Q46 1335 L9 Q47 1336 L9 Q48 1337 L9 Q49 1338 L9 Q50 1339 L9 Q51 1340 L9 Q52 1341 L9 Q53 1342 L9 Q54 1343 L9 Q55 1344 L9 Q56 1345 L9 Q57 1346 L9 Q58 1347 L9 Q59 1348 L9 Q60 1349 L9 Q61 1350 L9 Q62 1351 L9 Q63 1352 L9 Q64 1353 L9 Q65 1354 L9 Q66 1355 L9 Q67 1356 L9 Q68 1357 L9 Q69 1358 L9 Q70 1359 L9 Q71 1360 L9 Q72 1361 L9 Q73 1362 L9 Q74 1363 L9 Q75 1364 L9 Q76 1365 L9 Q77 1366 L9 Q78 1367 L9 Q79 1368 L9 Q80 1369 L9 Q81 1370 L9 Q82 1371 L9 Q83 1372 L9 Q84 1373 L9 Q85 1374 L9 Q86 1375 L9 Q87 1376 L9 Q88 1377 L9 Q89 1378 L9 Q90 1379 L9 Q91 1380 L9 Q92 1381 L9 Q93 1382 L9 Q94 1383 L9 Q95 1384 L9 Q96 1385 L9 Q97 1386 L9 Q98 1387 L9 Q99 1388 L9 Q100 1389 L9 Q101 1390 L9 Q102 1391 L9 Q103 1392 L9 Q104 1393 L9 Q105 1394 L9 Q106 1395 L9 Q107 1396 L9 Q108 1397 L9 Q109 1398 L9 Q110 1399 L9 Q111 1400 L9 Q112 1401 L9 Q113 1402 L9 Q114 1403 L9 Q115 1404 L9 Q116 1405 L9 Q117 1406 L9 Q118 1407 L9 Q119 1408 L9 Q120 1409 L9 Q121 1410 L9 Q122 1411 L9 Q123 1412 L9 Q124 1413 L9 Q125 1414 L9 Q126 1415 L9 Q127 1416 L9 Q128 1417 L9 Q129 1418 L9 Q130 1419 L9 Q131 1420 L9 Q132 1421 L9 Q133 1422 L9 Q134 1423 L9 Q135 1424 L9 Q136 1425 L9 Q137 1426 L9 Q138 1427 L9 Q139 1428 L9 Q140 1429 L9 Q141 1430 L9 Q142 1431 L9 Q143 1432 L9 Q144 1433 L9 Q145 1434 L9 Q146 1435 L9 Q147 1436 L9 Q148 1437 L9 Q149 1438 L9 Q150 1439 L9 Q151 1440 L9 Q152 1441 L9 Q153 1442 L9 Q154 1443 L9 Q155 1444 L9 Q156 1445 L9 Q157 1446 L9 Q158 1447 L9 Q159 1448 L9 Q160 1449 L9 Q161 1450 L10 Q1 1451 L10 Q2 1452 L10 Q3 1453 L10 Q4 1454 L10 Q5 1455 L10 Q6 1456 L10 Q7 1457 L10 Q8 1458 L10 Q9 1459 L10 Q10 1460 L10 Q11 1461 L10 Q12 1462 L10 Q13 1463 L10 Q14 1464 L10 Q15 1465 L10 Q16 1466 L10 Q17 1467 L10 Q18 1468 L10 Q19 1469 L10 Q20 1470 L10 Q21 1471 L10 Q22 1472 L10 Q23 1473 L10 Q24 1474 L10 Q25 1475 L10 Q26 1476 L10 Q27 1477 L10 Q28 1478 L10 Q29 1479 L10 Q30 1480 L10 Q31 1481 L10 Q32 1482 L10 Q33 1483 L10 Q34 1484 L10 Q35 1485 L10 Q36 1486 L10 Q37 1487 L10 Q38 1488 L10 Q39 1489 L10 Q40 1490 L10 Q41 1491 L10 Q42 1492 L10 Q43 1493 L10 Q44 1494 L10 Q45 1495 L10 Q46 1496 L10 Q47 1497 L10 Q48 1498 L10 Q49 1499 L10 Q50 1500 L10 Q51 1501 L10 Q52 1502 L10 Q53 1503 L10 Q54 1504 L10 Q55 1505 L10 Q56 1506 L10 Q57 1507 L10 Q58 1508 L10 Q59 1509 L10 Q60 1510 L10 Q61 1511 L10 Q62 1512 L10 Q63 1513 L10 Q64 1514 L10 Q65 1515 L10 Q66 1516 L10 Q67 1517 L10 Q68 1518 L10 Q69 1519 L10 Q70 1520 L10 Q71 1521 L10 Q72 1522 L10 Q73 1523 L10 Q74 1524 L10 Q75 1525 L10 Q76 1526 L10 Q77 1527 L10 Q78 1528 L10 Q79 1529 L10 Q80 1530 L10 Q81 1531 L10 Q82 1532 L10 Q83 1533 L10 Q84 1534 L10 Q85 1535 L10 Q86 1536 L10 Q87 1537 L10 Q88 1538 L10 Q89 1539 L10 Q90 1540 L10 Q91 1541 L10 Q92 1542 L10 Q93 1543 L10 Q94 1544 L10 Q95 1545 L10 Q96 1546 L10 Q97 1547 L10 Q98 1548 L10 Q99 1549 L10 Q100 1550 L10 Q101 1551 L10 Q102 1552 L10 Q103 1553 L10 Q104 1554 L10 Q105 1555 L10 Q106 1556 L10 Q107 1557 L10 Q108 1558 L10 Q109 1559 L10 Q110 1560 L10 Q111 1561 L10 Q112 1562 L10 Q113 1563 L10 Q114 1564 L10 Q115 1565 L10 Q116 1566 L10 Q117 1567 L10 Q118 1568 L10 Q119 1569 L10 Q120 1570 L10 Q121 1571 L10 Q122 1572 L10 Q123 1573 L10 Q124 1574 L10 Q125 1575 L10 Q126 1576 L10 Q127 1577 L10 Q128 1578 L10 Q129 1579 L10 Q130 1580 L10 Q131 1581 L10 Q132 1582 L10 Q133 1583 L10 Q134 1584 L10 Q135 1585 L10 Q136 1586 L10 Q137 1587 L10 Q138 1588 L10 Q139 1589 L10 Q140 1590 L10 Q141 1591 L10 Q142 1592 L10 Q143 1593 L10 Q144 1594 L10 Q145 1595 L10 Q146 1596 L10 Q147 1597 L10 Q148 1598 L10 Q149 1599 L10 Q150 1600 L10 Q151 1601 L10 Q152 1602 L10 Q153 1603 L10 Q154 1604 L10 Q155 1605 L10 Q156 1606 L10 Q157 1607 L10 Q158 1608 L10 Q159 1609 L10 Q160 1610 L10 Q161 1611 L11 Q1 1612 L11 Q2 1613 L11 Q3 1614 L11 Q4 1615 L11 Q5 1616 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Q113 2368 L15 Q114 2369 L15 Q115 2370 L15 Q116 2371 L15 Q117 2372 L15 Q118 2373 L15 Q119 2374 L15 Q120 2375 L15 Q121 2376 L15 Q122 2377 L15 Q123 2378 L15 Q124 2379 L15 Q125 2380 L15 Q126 2381 L15 Q127 2382 L15 Q128 2383 L15 Q129 2384 L15 Q130 2385 L15 Q131 2386 L15 Q132 2387 L15 Q133 2388 L15 Q134 2389 L15 Q135 2390 L15 Q136 2391 L15 Q137 2392 L15 Q138 2393 L15 Q139 2394 L15 Q140 2395 L15 Q141 2396 L15 Q142 2397 L15 Q143 2398 L15 Q144 2399 L15 Q145 2400 L15 Q146 2401 L15 Q147 2402 L15 Q148 2403 L15 Q149 2404 L15 Q150 2405 L15 Q151 2406 L15 Q152 2407 L15 Q153 2408 L15 Q154 2409 L15 Q155 2410 L15 Q156 2411 L15 Q157 2412 L15 Q158 2413 L15 Q159 2414 L15 Q160 2415 L15 Q161 2416 L16 Q1 2417 L16 Q2 2418 L16 Q3 2419 L16 Q4 2420 L16 Q5 2421 L16 Q6 2422 L16 Q7 2423 L16 Q8 2424 L16 Q9 2425 L16 Q10 2426 L16 Q11 2427 L16 Q12 2428 L16 Q13 2429 L16 Q14 2430 L16 Q15 2431 L16 Q16 2432 L16 Q17 2433 L16 Q18 2434 L16 Q19 2435 L16 Q20 2436 L16 Q21 2437 L16 Q22 2438 L16 Q23 2439 L16 Q24 2440 L16 Q25 2441 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4015 L25 Q151 4016 L25 Q152 4017 L25 Q153 4018 L25 Q154 4019 L25 Q155 4020 L25 Q156 4021 L25 Q157 4022 L25 Q158 4023 L25 Q159 4024 L25 Q160 4025 L25 Q161 4026 L26 Q1 4027 L26 Q2 4028 L26 Q3 4029 L26 Q4 4030 L26 Q5 4031 L26 Q6 4032 L26 Q7 4033 L26 Q8 4034 L26 Q9 4035 L26 Q10 4036 L26 Q11 4037 L26 Q12 4038 L26 Q13 4039 L26 Q14 4040 L26 Q15 4041 L26 Q16 4042 L26 Q17 4043 L26 Q18 4044 L26 Q19 4045 L26 Q20 4046 L26 Q21 4047 L26 Q22 4048 L26 Q23 4049 L26 Q24 4050 L26 Q25 4051 L26 Q26 4052 L26 Q27 4053 L26 Q28 4054 L26 Q29 4055 L26 Q30 4056 L26 Q31 4057 L26 Q32 4058 L26 Q33 4059 L26 Q34 4060 L26 Q35 4061 L26 Q36 4062 L26 Q37 4063 L26 Q38 4064 L26 Q39 4065 L26 Q40 4066 L26 Q41 4067 L26 Q42 4068 L26 Q43 4069 L26 Q44 4070 L26 Q45 4071 L26 Q46 4072 L26 Q47 4073 L26 Q48 4074 L26 Q49 4075 L26 Q50 4076 L26 Q51 4077 L26 Q52 4078 L26 Q53 4079 L26 Q54 4080 L26 Q55 4081 L26 Q56 4082 L26 Q57 4083 L26 Q58 4084 L26 Q59 4085 L26 Q60 4086 L26 Q61 4087 L26 Q62 4088 L26 Q63 4089 L26 Q64 4090 L26 Q65 4091 L26 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L62 Q42 9864 L62 Q43 9865 L62 Q44 9866 L62 Q45 9867 L62 Q46 9868 L62 Q47 9869 L62 Q48 9870 L62 Q49 9871 L62 Q50 9872 L62 Q51 9873 L62 Q52 9874 L62 Q53 9875 L62 Q54 9876 L62 Q55 9877 L62 Q56 9878 L62 Q57 9879 L62 Q58 9880 L62 Q59 9881 L62 Q60 9882 L62 Q61 9883 L62 Q62 9884 L62 Q63 9885 L62 Q64 9886 L62 Q65 9887 L62 Q66 9888 L62 Q67 9889 L62 Q68 9890 L62 Q69 9891 L62 Q70 9892 L62 Q71 9893 L62 Q72 9894 L62 Q73 9895 L62 Q74 9896 L62 Q75 9897 L62 Q76 9898 L62 Q77 9899 L62 Q78 9900 L62 Q79 9901 L62 Q80 9902 L62 Q81 9903 L62 Q82 9904 L62 Q83 9905 L62 Q84 9906 L62 Q85 9907 L62 Q86 9908 L62 Q87 9909 L62 Q88 9910 L62 Q89 9911 L62 Q90 9912 L62 Q91 9913 L62 Q92 9914 L62 Q93 9915 L62 Q94 9916 L62 Q95 9917 L62 Q96 9918 L62 Q97 9919 L62 Q98 9920 L62 Q99 9921 L62 Q100 9922 L62 Q101 9923 L62 Q102 9924 L62 Q103 9925 L62 Q104 9926 L62 Q105 9927 L62 Q106 9928 L62 Q107 9929 L62 Q108 9930 L62 Q109 9931 L62 Q110 9932 L62 Q111 9933 L62 Q112 9934 L62 Q113 9935 L62 Q114 9936 L62 Q115 9937 L62 Q116 9938 L62 Q117 9939 L62 Q118 9940 L62 Q119 9941 L62 Q120 9942 L62 Q121 9943 L62 Q122 9944 L62 Q123 9945 L62 Q124 9946 L62 Q125 9947 L62 Q126 9948 L62 Q127 9949 L62 Q128 9950 L62 Q129 9951 L62 Q130 9952 L62 Q131 9953 L62 Q132 9954 L62 Q133 9955 L62 Q134 9956 L62 Q135 9957 L62 Q136 9958 L62 Q137 9959 L62 Q138 9960 L62 Q139 9961 L62 Q140 9962 L62 Q141 9963 L62 Q142 9964 L62 Q143 9965 L62 Q144 9966 L62 Q145 9967 L62 Q146 9968 L62 Q147 9969 L62 Q148 9970 L62 Q149 9971 L62 Q150 9972 L62 Q151 9973 L62 Q152 9974 L62 Q153 9975 L62 Q154 9976 L62 Q155 9977 L62 Q156 9978 L62 Q157 9979 L62 Q158 9980 L62 Q159 9981 L62 Q160 9982 L62 Q161 9983 L63 Q1 9984 L63 Q2 9985 L63 Q3 9986 L63 Q4 9987 L63 Q5 9988 L63 Q6 9989 L63 Q7 9990 L63 Q8 9991 L63 Q9 9992 L63 Q10 9993 L63 Q11 9994 L63 Q12 9995 L63 Q13 9996 L63 Q14 9997 L63 Q15 9998 L63 Q16 9999 L63 Q17 10000 L63 Q18 10001 L63 Q19 10002 L63 Q20 10003 L63 Q21 10004 L63 Q22 10005 L63 Q23 10006 L63 Q24 10007 L63 Q25 10008 L63 Q26 10009 L63 Q27 10010 L63 Q28 10011 L63 Q29 10012 L63 Q30 10013 L63 Q31 10014 L63 Q32 10015 L63 Q33 10016 L63 Q34 10017 L63 Q35 10018 L63 Q36 10019 L63 Q37 10020 L63 Q38 10021 L63 Q39 10022 L63 Q40 10023 L63 Q41 10024 L63 Q42 10025 L63 Q43 10026 L63 Q44 10027 L63 Q45 10028 L63 Q46 10029 L63 Q47 10030 L63 Q48 10031 L63 Q49 10032 L63 Q50 10033 L63 Q51 10034 L63 Q52 10035 L63 Q53 10036 L63 Q54 10037 L63 Q55 10038 L63 Q56 10039 L63 Q57 10040 L63 Q58 10041 L63 Q59 10042 L63 Q60 10043 L63 Q61 10044 L63 Q62 10045 L63 Q63 10046 L63 Q64 10047 L63 Q65 10048 L63 Q66 10049 L63 Q67 10050 L63 Q68 10051 L63 Q69 10052 L63 Q70 10053 L63 Q71 10054 L63 Q72 10055 L63 Q73 10056 L63 Q74 10057 L63 Q75 10058 L63 Q76 10059 L63 Q77 10060 L63 Q78 10061 L63 Q79 10062 L63 Q80 10063 L63 Q81 10064 L63 Q82 10065 L63 Q83 10066 L63 Q84 10067 L63 Q85 10068 L63 Q86 10069 L63 Q87 10070 L63 Q88 10071 L63 Q89 10072 L63 Q90 10073 L63 Q91 10074 L63 Q92 10075 L63 Q93 10076 L63 Q94 10077 L63 Q95 10078 L63 Q96 10079 L63 Q97 10080 L63 Q98 10081 L63 Q99 10082 L63 Q100 10083 L63 Q101 10084 L63 Q102 10085 L63 Q103 10086 L63 Q104 10087 L63 Q105 10088 L63 Q106 10089 L63 Q107 10090 L63 Q108 10091 L63 Q109 10092 L63 Q110 10093 L63 Q111 10094 L63 Q112 10095 L63 Q113 10096 L63 Q114 10097 L63 Q115 10098 L63 Q116 10099 L63 Q117 10100 L63 Q118 10101 L63 Q119 10102 L63 Q120 10103 L63 Q121 10104 L63 Q122 10105 L63 Q123 10106 L63 Q124 10107 L63 Q125 10108 L63 Q126 10109 L63 Q127 10110 L63 Q128 10111 L63 Q129 10112 L63 Q130 10113 L63 Q131 10114 L63 Q132 10115 L63 Q133 10116 L63 Q134 10117 L63 Q135 10118 L63 Q136 10119 L63 Q137 10120 L63 Q138 10121 L63 Q139 10122 L63 Q140 10123 L63 Q141 10124 L63 Q142 10125 L63 Q143 10126 L63 Q144 10127 L63 Q145 10128 L63 Q146 10129 L63 Q147 10130 L63 Q148 10131 L63 Q149 10132 L63 Q150 10133 L63 Q151 10134 L63 Q152 10135 L63 Q153 10136 L63 Q154 10137 L63 Q155 10138 L63 Q156 10139 L63 Q157 10140 L63 Q158 10141 L63 Q159 10142 L63 Q160 10143 L63 Q161 10144 L64 Q1 10145 L64 Q2 10146 L64 Q3 10147 L64 Q4 10148 L64 Q5 10149 L64 Q6 10150 L64 Q7 10151 L64 Q8 10152 L64 Q9 10153 L64 Q10 10154 L64 Q11 10155 L64 Q12 10156 L64 Q13 10157 L64 Q14 10158 L64 Q15 10159 L64 Q16 10160 L64 Q17 10161 L64 Q18 10162 L64 Q19 10163 L64 Q20 10164 L64 Q21 10165 L64 Q22 10166 L64 Q23 10167 L64 Q24 10168 L64 Q25 10169 L64 Q26 10170 L64 Q27 10171 L64 Q28 10172 L64 Q29 10173 L64 Q30 10174 L64 Q31 10175 L64 Q32 10176 L64 Q33 10177 L64 Q34 10178 L64 Q35 10179 L64 Q36 10180 L64 Q37 10181 L64 Q38 10182 L64 Q39 10183 L64 Q40 10184 L64 Q41 10185 L64 Q42 10186 L64 Q43 10187 L64 Q44 10188 L64 Q45 10189 L64 Q46 10190 L64 Q47 10191 L64 Q48 10192 L64 Q49 10193 L64 Q50 10194 L64 Q51 10195 L64 Q52 10196 L64 Q53 10197 L64 Q54 10198 L64 Q55 10199 L64 Q56 10200 L64 Q57 10201 L64 Q58 10202 L64 Q59 10203 L64 Q60 10204 L64 Q61 10205 L64 Q62 10206 L64 Q63 10207 L64 Q64 10208 L64 Q65 10209 L64 Q66 10210 L64 Q67 10211 L64 Q68 10212 L64 Q69 10213 L64 Q70 10214 L64 Q71 10215 L64 Q72 10216 L64 Q73 10217 L64 Q74 10218 L64 Q75 10219 L64 Q76 10220 L64 Q77 10221 L64 Q78 10222 L64 Q79 10223 L64 Q80 10224 L64 Q81 10225 L64 Q82 10226 L64 Q83 10227 L64 Q84 10228 L64 Q85 10229 L64 Q86 10230 L64 Q87 10231 L64 Q88 10232 L64 Q89 10233 L64 Q90 10234 L64 Q91 10235 L64 Q92 10236 L64 Q93 10237 L64 Q94 10238 L64 Q95 10239 L64 Q96 10240 L64 Q97 10241 L64 Q98 10242 L64 Q99 10243 L64 Q100 10244 L64 Q101 10245 L64 Q102 10246 L64 Q103 10247 L64 Q104 10248 L64 Q105 10249 L64 Q106 10250 L64 Q107 10251 L64 Q108 10252 L64 Q109 10253 L64 Q110 10254 L64 Q111 10255 L64 Q112 10256 L64 Q113 10257 L64 Q114 10258 L64 Q115 10259 L64 Q116 10260 L64 Q117 10261 L64 Q118 10262 L64 Q119 10263 L64 Q120 10264 L64 Q121 10265 L64 Q122 10266 L64 Q123 10267 L64 Q124 10268 L64 Q125 10269 L64 Q126 10270 L64 Q127 10271 L64 Q128 10272 L64 Q129 10273 L64 Q130 10274 L64 Q131 10275 L64 Q132 10276 L64 Q133 10277 L64 Q134 10278 L64 Q135 10279 L64 Q136 10280 L64 Q137 10281 L64 Q138 10282 L64 Q139 10283 L64 Q140 10284 L64 Q141 10285 L64 Q142 10286 L64 Q143 10287 L64 Q144 10288 L64 Q145 10289 L64 Q146 10290 L64 Q147 10291 L64 Q148 10292 L64 Q149 10293 L64 Q150 10294 L64 Q151 10295 L64 Q152 10296 L64 Q153 10297 L64 Q154 10298 L64 Q155 10299 L64 Q156 10300 L64 Q157 10301 L64 Q158 10302 L64 Q159 10303 L64 Q160 10304 L64 Q161 10305 L65 Q1 10306 L65 Q2 10307 L65 Q3 10308 L65 Q4 10309 L65 Q5 10310 L65 Q6 10311 L65 Q7 10312 L65 Q8 10313 L65 Q9 10314 L65 Q10 10315 L65 Q11 10316 L65 Q12 10317 L65 Q13 10318 L65 Q14 10319 L65 Q15 10320 L65 Q16 10321 L65 Q17 10322 L65 Q18 10323 L65 Q19 10324 L65 Q20 10325 L65 Q21 10326 L65 Q22 10327 L65 Q23 10328 L65 Q24 10329 L65 Q25 10330 L65 Q26 10331 L65 Q27 10332 L65 Q28 10333 L65 Q29 10334 L65 Q30 10335 L65 Q31 10336 L65 Q32 10337 L65 Q33 10338 L65 Q34 10339 L65 Q35 10340 L65 Q36 10341 L65 Q37 10342 L65 Q38 10343 L65 Q39 10344 L65 Q40 10345 L65 Q41 10346 L65 Q42 10347 L65 Q43 10348 L65 Q44 10349 L65 Q45 10350 L65 Q46 10351 L65 Q47 10352 L65 Q48 10353 L65 Q49 10354 L65 Q50 10355 L65 Q51 10356 L65 Q52 10357 L65 Q53 10358 L65 Q54 10359 L65 Q55 10360 L65 Q56 10361 L65 Q57 10362 L65 Q58 10363 L65 Q59 10364 L65 Q60 10365 L65 Q61 10366 L65 Q62 10367 L65 Q63 10368 L65 Q64 10369 L65 Q65 10370 L65 Q66 10371 L65 Q67 10372 L65 Q68 10373 L65 Q69 10374 L65 Q70 10375 L65 Q71 10376 L65 Q72 10377 L65 Q73 10378 L65 Q74 10379 L65 Q75 10380 L65 Q76 10381 L65 Q77 10382 L65 Q78 10383 L65 Q79 10384 L65 Q80 10385 L65 Q81 10386 L65 Q82 10387 L65 Q83 10388 L65 Q84 10389 L65 Q85 10390 L65 Q86 10391 L65 Q87 10392 L65 Q88 10393 L65 Q89 10394 L65 Q90 10395 L65 Q91 10396 L65 Q92 10397 L65 Q93 10398 L65 Q94 10399 L65 Q95 10400 L65 Q96 10401 L65 Q97 10402 L65 Q98 10403 L65 Q99 10404 L65 Q100 10405 L65 Q101 10406 L65 Q102 10407 L65 Q103 10408 L65 Q104 10409 L65 Q105 10410 L65 Q106 10411 L65 Q107 10412 L65 Q108 10413 L65 Q109 10414 L65 Q110 10415 L65 Q111 10416 L65 Q112 10417 L65 Q113 10418 L65 Q114 10419 L65 Q115 10420 L65 Q116 10421 L65 Q117 10422 L65 Q118 10423 L65 Q119 10424 L65 Q120 10425 L65 Q121 10426 L65 Q122 10427 L65 Q123 10428 L65 Q124 10429 L65 Q125 10430 L65 Q126 10431 L65 Q127 10432 L65 Q128 10433 L65 Q129 10434 L65 Q130 10435 L65 Q131 10436 L65 Q132 10437 L65 Q133 10438 L65 Q134 10439 L65 Q135 10440 L65 Q136 10441 L65 Q137 10442 L65 Q138 10443 L65 Q139 10444 L65 Q140 10445 L65 Q141 10446 L65 Q142 10447 L65 Q143 10448 L65 Q144 10449 L65 Q145 10450 L65 Q146 10451 L65 Q147 10452 L65 Q148 10453 L65 Q149 10454 L65 Q150 10455 L65 Q151 10456 L65 Q152 10457 L65 Q153 10458 L65 Q154 10459 L65 Q155 10460 L65 Q156 10461 L65 Q157 10462 L65 Q158 10463 L65 Q159 10464 L65 Q160 10465 L65 Q161 10466 L66 Q1 10467 L66 Q2 10468 L66 Q3 10469 L66 Q4 10470 L66 Q5 10471 L66 Q6 10472 L66 Q7 10473 L66 Q8 10474 L66 Q9 10475 L66 Q10 10476 L66 Q11 10477 L66 Q12 10478 L66 Q13 10479 L66 Q14 10480 L66 Q15 10481 L66 Q16 10482 L66 Q17 10483 L66 Q18 10484 L66 Q19 10485 L66 Q20 10486 L66 Q21 10487 L66 Q22 10488 L66 Q23 10489 L66 Q24 10490 L66 Q25 10491 L66 Q26 10492 L66 Q27 10493 L66 Q28 10494 L66 Q29 10495 L66 Q30 10496 L66 Q31 10497 L66 Q32 10498 L66 Q33 10499 L66 Q34 10500 L66 Q35 10501 L66 Q36 10502 L66 Q37 10503 L66 Q38 10504 L66 Q39 10505 L66 Q40 10506 L66 Q41 10507 L66 Q42 10508 L66 Q43 10509 L66 Q44 10510 L66 Q45 10511 L66 Q46 10512 L66 Q47 10513 L66 Q48 10514 L66 Q49 10515 L66 Q50 10516 L66 Q51 10517 L66 Q52 10518 L66 Q53 10519 L66 Q54 10520 L66 Q55 10521 L66 Q56 10522 L66 Q57 10523 L66 Q58 10524 L66 Q59 10525 L66 Q60 10526 L66 Q61 10527 L66 Q62 10528 L66 Q63 10529 L66 Q64 10530 L66 Q65 10531 L66 Q66 10532 L66 Q67 10533 L66 Q68 10534 L66 Q69 10535 L66 Q70 10536 L66 Q71 10537 L66 Q72 10538 L66 Q73 10539 L66 Q74 10540 L66 Q75 10541 L66 Q76 10542 L66 Q77 10543 L66 Q78 10544 L66 Q79 10545 L66 Q80 10546 L66 Q81 10547 L66 Q82 10548 L66 Q83 10549 L66 Q84 10550 L66 Q85 10551 L66 Q86 10552 L66 Q87 10553 L66 Q88 10554 L66 Q89 10555 L66 Q90 10556 L66 Q91 10557 L66 Q92 10558 L66 Q93 10559 L66 Q94 10560 L66 Q95 10561 L66 Q96 10562 L66 Q97 10563 L66 Q98 10564 L66 Q99 10565 L66 Q100 10566 L66 Q101 10567 L66 Q102 10568 L66 Q103 10569 L66 Q104 10570 L66 Q105 10571 L66 Q106 10572 L66 Q107 10573 L66 Q108 10574 L66 Q109 10575 L66 Q110 10576 L66 Q111 10577 L66 Q112 10578 L66 Q113 10579 L66 Q114 10580 L66 Q115 10581 L66 Q116 10582 L66 Q117 10583 L66 Q118 10584 L66 Q119 10585 L66 Q120 10586 L66 Q121 10587 L66 Q122 10588 L66 Q123 10589 L66 Q124 10590 L66 Q125 10591 L66 Q126 10592 L66 Q127 10593 L66 Q128 10594 L66 Q129 10595 L66 Q130 10596 L66 Q131 10597 L66 Q132 10598 L66 Q133 10599 L66 Q134 10600 L66 Q135 10601 L66 Q136 10602 L66 Q137 10603 L66 Q138 10604 L66 Q139 10605 L66 Q140 10606 L66 Q141 10607 L66 Q142 10608 L66 Q143 10609 L66 Q144 10610 L66 Q145 10611 L66 Q146 10612 L66 Q147 10613 L66 Q148 10614 L66 Q149 10615 L66 Q150 10616 L66 Q151 10617 L66 Q152 10618 L66 Q153 10619 L66 Q154 10620 L66 Q155 10621 L66 Q156 10622 L66 Q157 10623 L66 Q158 10624 L66 Q159 10625 L66 Q160 10626 L66 Q161 10627 L67 Q1 10628 L67 Q2 10629 L67 Q3 10630 L67 Q4 10631 L67 Q5 10632 L67 Q6 10633 L67 Q7 10634 L67 Q8 10635 L67 Q9 10636 L67 Q10 10637 L67 Q11 10638 L67 Q12 10639 L67 Q13 10640 L67 Q14 10641 L67 Q15 10642 L67 Q16 10643 L67 Q17 10644 L67 Q18 10645 L67 Q19 10646 L67 Q20 10647 L67 Q21 10648 L67 Q22 10649 L67 Q23 10650 L67 Q24 10651 L67 Q25 10652 L67 Q26 10653 L67 Q27 10654 L67 Q28 10655 L67 Q29 10656 L67 Q30 10657 L67 Q31 10658 L67 Q32 10659 L67 Q33 10660 L67 Q34 10661 L67 Q35 10662 L67 Q36 10663 L67 Q37 10664 L67 Q38 10665 L67 Q39 10666 L67 Q40 10667 L67 Q41 10668 L67 Q42 10669 L67 Q43 10670 L67 Q44 10671 L67 Q45 10672 L67 Q46 10673 L67 Q47 10674 L67 Q48 10675 L67 Q49 10676 L67 Q50 10677 L67 Q51 10678 L67 Q52 10679 L67 Q53 10680 L67 Q54 10681 L67 Q55 10682 L67 Q56 10683 L67 Q57 10684 L67 Q58 10685 L67 Q59 10686 L67 Q60 10687 L67 Q61 10688 L67 Q62 10689 L67 Q63 10690 L67 Q64 10691 L67 Q65 10692 L67 Q66 10693 L67 Q67 10694 L67 Q68 10695 L67 Q69 10696 L67 Q70 10697 L67 Q71 10698 L67 Q72 10699 L67 Q73 10700 L67 Q74 10701 L67 Q75 10702 L67 Q76 10703 L67 Q77 10704 L67 Q78 10705 L67 Q79 10706 L67 Q80 10707 L67 Q81 10708 L67 Q82 10709 L67 Q83 10710 L67 Q84 10711 L67 Q85 10712 L67 Q86 10713 L67 Q87 10714 L67 Q88 10715 L67 Q89 10716 L67 Q90 10717 L67 Q91 10718 L67 Q92 10719 L67 Q93 10720 L67 Q94 10721 L67 Q95 10722 L67 Q96 10723 L67 Q97 10724 L67 Q98 10725 L67 Q99 10726 L67 Q100 10727 L67 Q101 10728 L67 Q102 10729 L67 Q103 10730 L67 Q104 10731 L67 Q105 10732 L67 Q106 10733 L67 Q107 10734 L67 Q108 10735 L67 Q109 10736 L67 Q110 10737 L67 Q111 10738 L67 Q112 10739 L67 Q113 10740 L67 Q114 10741 L67 Q115 10742 L67 Q116 10743 L67 Q117 10744 L67 Q118 10745 L67 Q119 10746 L67 Q120 10747 L67 Q121 10748 L67 Q122 10749 L67 Q123 10750 L67 Q124 10751 L67 Q125 10752 L67 Q126 10753 L67 Q127 10754 L67 Q128 10755 L67 Q129 10756 L67 Q130 10757 L67 Q131 10758 L67 Q132 10759 L67 Q133 10760 L67 Q134 10761 L67 Q135 10762 L67 Q136 10763 L67 Q137 10764 L67 Q138 10765 L67 Q139 10766 L67 Q140 10767 L67 Q141 10768 L67 Q142 10769 L67 Q143 10770 L67 Q144 10771 L67 Q145 10772 L67 Q146 10773 L67 Q147 10774 L67 Q148 10775 L67 Q149 10776 L67 Q150 10777 L67 Q151 10778 L67 Q152 10779 L67 Q153 10780 L67 Q154 10781 L67 Q155 10782 L67 Q156 10783 L67 Q157 10784 L67 Q158 10785 L67 Q159 10786 L67 Q160 10787 L67 Q161 10788 L68 Q1 10789 L68 Q2 10790 L68 Q3 10791 L68 Q4 10792 L68 Q5 10793 L68 Q6 10794 L68 Q7 10795 L68 Q8 10796 L68 Q9 10797 L68 Q10 10798 L68 Q11 10799 L68 Q12 10800 L68 Q13 10801 L68 Q14 10802 L68 Q15 10803 L68 Q16 10804 L68 Q17 10805 L68 Q18 10806 L68 Q19 10807 L68 Q20 10808 L68 Q21 10809 L68 Q22 10810 L68 Q23 10811 L68 Q24 10812 L68 Q25 10813 L68 Q26 10814 L68 Q27 10815 L68 Q28 10816 L68 Q29 10817 L68 Q30 10818 L68 Q31 10819 L68 Q32 10820 L68 Q33 10821 L68 Q34 10822 L68 Q35 10823 L68 Q36 10824 L68 Q37 10825 L68 Q38 10826 L68 Q39 10827 L68 Q40 10828 L68 Q41 10829 L68 Q42 10830 L68 Q43 10831 L68 Q44 10832 L68 Q45 10833 L68 Q46 10834 L68 Q47 10835 L68 Q48 10836 L68 Q49 10837 L68 Q50 10838 L68 Q51 10839 L68 Q52 10840 L68 Q53 10841 L68 Q54 10842 L68 Q55 10843 L68 Q56 10844 L68 Q57 10845 L68 Q58 10846 L68 Q59 10847 L68 Q60 10848 L68 Q61 10849 L68 Q62 10850 L68 Q63 10851 L68 Q64 10852 L68 Q65 10853 L68 Q66 10854 L68 Q67 10855 L68 Q68 10856 L68 Q69 10857 L68 Q70 10858 L68 Q71 10859 L68 Q72 10860 L68 Q73 10861 L68 Q74 10862 L68 Q75 10863 L68 Q76 10864 L68 Q77 10865 L68 Q78 10866 L68 Q79 10867 L68 Q80 10868 L68 Q81 10869 L68 Q82 10870 L68 Q83 10871 L68 Q84 10872 L68 Q85 10873 L68 Q86 10874 L68 Q87 10875 L68 Q88 10876 L68 Q89 10877 L68 Q90 10878 L68 Q91 10879 L68 Q92 10880 L68 Q93 10881 L68 Q94 10882 L68 Q95 10883 L68 Q96 10884 L68 Q97 10885 L68 Q98 10886 L68 Q99 10887 L68 Q100 10888 L68 Q101 10889 L68 Q102 10890 L68 Q103 10891 L68 Q104 10892 L68 Q105 10893 L68 Q106 10894 L68 Q107 10895 L68 Q108 10896 L68 Q109 10897 L68 Q110 10898 L68 Q111 10899 L68 Q112 10900 L68 Q113 10901 L68 Q114 10902 L68 Q115 10903 L68 Q116 10904 L68 Q117 10905 L68 Q118 10906 L68 Q119 10907 L68 Q120 10908 L68 Q121 10909 L68 Q122 10910 L68 Q123 10911 L68 Q124 10912 L68 Q125 10913 L68 Q126 10914 L68 Q127 10915 L68 Q128 10916 L68 Q129 10917 L68 Q130 10918 L68 Q131 10919 L68 Q132 10920 L68 Q133 10921 L68 Q134 10922 L68 Q135 10923 L68 Q136 10924 L68 Q137 10925 L68 Q138 10926 L68 Q139 10927 L68 Q140 10928 L68 Q141 10929 L68 Q142 10930 L68 Q143 10931 L68 Q144 10932 L68 Q145 10933 L68 Q146 10934 L68 Q147 10935 L68 Q148 10936 L68 Q149 10937 L68 Q150 10938 L68 Q151 10939 L68 Q152 10940 L68 Q153 10941 L68 Q154 10942 L68 Q155 10943 L68 Q156 10944 L68 Q157 10945 L68 Q158 10946 L68 Q159 10947 L68 Q160 10948 L68 Q161 10949 L69 Q1 10950 L69 Q2 10951 L69 Q3 10952 L69 Q4 10953 L69 Q5 10954 L69 Q6 10955 L69 Q7 10956 L69 Q8 10957 L69 Q9 10958 L69 Q10 10959 L69 Q11 10960 L69 Q12 10961 L69 Q13 10962 L69 Q14 10963 L69 Q15 10964 L69 Q16 10965 L69 Q17 10966 L69 Q18 10967 L69 Q19 10968 L69 Q20 10969 L69 Q21 10970 L69 Q22 10971 L69 Q23 10972 L69 Q24 10973 L69 Q25 10974 L69 Q26 10975 L69 Q27 10976 L69 Q28 10977 L69 Q29 10978 L69 Q30 10979 L69 Q31 10980 L69 Q32 10981 L69 Q33 10982 L69 Q34 10983 L69 Q35 10984 L69 Q36 10985 L69 Q37 10986 L69 Q38 10987 L69 Q39 10988 L69 Q40 10989 L69 Q41 10990 L69 Q42 10991 L69 Q43 10992 L69 Q44 10993 L69 Q45 10994 L69 Q46 10995 L69 Q47 10996 L69 Q48 10997 L69 Q49 10998 L69 Q50 10999 L69 Q51 11000 L69 Q52 11001 L69 Q53 11002 L69 Q54 11003 L69 Q55 11004 L69 Q56 11005 L69 Q57 11006 L69 Q58 11007 L69 Q59 11008 L69 Q60 11009 L69 Q61 11010 L69 Q62 11011 L69 Q63 11012 L69 Q64 11013 L69 Q65 11014 L69 Q66 11015 L69 Q67 11016 L69 Q68 11017 L69 Q69 11018 L69 Q70 11019 L69 Q71 11020 L69 Q72 11021 L69 Q73 11022 L69 Q74 11023 L69 Q75 11024 L69 Q76 11025 L69 Q77 11026 L69 Q78 11027 L69 Q79 11028 L69 Q80 11029 L69 Q81 11030 L69 Q82 11031 L69 Q83 11032 L69 Q84 11033 L69 Q85 11034 L69 Q86 11035 L69 Q87 11036 L69 Q88 11037 L69 Q89 11038 L69 Q90 11039 L69 Q91 11040 L69 Q92 11041 L69 Q93 11042 L69 Q94 11043 L69 Q95 11044 L69 Q96 11045 L69 Q97 11046 L69 Q98 11047 L69 Q99 11048 L69 Q100 11049 L69 Q101 11050 L69 Q102 11051 L69 Q103 11052 L69 Q104 11053 L69 Q105 11054 L69 Q106 11055 L69 Q107 11056 L69 Q108 11057 L69 Q109 11058 L69 Q110 11059 L69 Q111 11060 L69 Q112 11061 L69 Q113 11062 L69 Q114 11063 L69 Q115 11064 L69 Q116 11065 L69 Q117 11066 L69 Q118 11067 L69 Q119 11068 L69 Q120 11069 L69 Q121 11070 L69 Q122 11071 L69 Q123 11072 L69 Q124 11073 L69 Q125 11074 L69 Q126 11075 L69 Q127 11076 L69 Q128 11077 L69 Q129 11078 L69 Q130 11079 L69 Q131 11080 L69 Q132 11081 L69 Q133 11082 L69 Q134 11083 L69 Q135 11084 L69 Q136 11085 L69 Q137 11086 L69 Q138 11087 L69 Q139 11088 L69 Q140 11089 L69 Q141 11090 L69 Q142 11091 L69 Q143 11092 L69 Q144 11093 L69 Q145 11094 L69 Q146 11095 L69 Q147 11096 L69 Q148 11097 L69 Q149 11098 L69 Q150 11099 L69 Q151 11100 L69 Q152 11101 L69 Q153 11102 L69 Q154 11103 L69 Q155 11104 L69 Q156 11105 L69 Q157 11106 L69 Q158 11107 L69 Q159 11108 L69 Q160 11109 L69 Q161

A specific example of another embodiment of the compound of the invention includes a compound represented by formula (11):

or a pharmaceutically acceptable salt thereof. In formula (11), R^(G) is a hydroxyl group, a thiol group, or —NHR^(a1), R^(a1), X, R¹, R², R³, R⁴, R⁶¹, R⁶², R⁶³, and R⁶⁴ are defined the same as the definition herein (e.g., any one of items 1 to 16 and items B1 to B15), and formula (1a) is defined the same as the definition herein.

A specific example of another embodiment of the compound of the invention includes a compound represented by formula (12):

or a pharmaceutically acceptable salt thereof. In formula (12), R^(G) is a hydroxyl group, a thiol group, or —NHR^(a1), R^(a1), X, R¹, R², R³ and R⁴ are defined the same as the definition herein (e.g., item 16 or 17 or item B16 or B17). A compound of formula (12) is in an interchangeable relationship with, and thus can be biologically equivalent with, a compound of formula (1a) or (3a) due to an equilibrium reaction in an aqueous solution or in the body.

In some embodiments, X and R^(G) are hydroxyl groups, R⁴ is a carboxyl group, and ring A is an optionally substituted 4- to 6-membered nitrogen-containing non-aryl heterocycle.

In some embodiments, R^(G) is a hydroxyl group or a thiol group. In some embodiments, R^(G) is a hydroxyl group.

In some embodiments, X is a hydroxyl group or a C₁₋₆ alkoxy group. In some embodiments, X is a hydroxyl group.

In some embodiments, m is 1 or 2, n is 1 or 2, and m+n is 2 or 3. In some embodiments, m is 1, and n is 1.

In some embodiments, L³ is defined the same as the definition herein (e.g., item 25 or 26 or B24 or B25).

In some embodiments, L⁴ and R⁵ are defined the same as the definition herein (e.g., any one of items 27 and 66 to 100 and B26 and B60 to B89).

A specific example of another embodiment of the compound of the invention includes a compound represented by formula (13):

or a pharmaceutically acceptable salt thereof. In formula (13), X, Y, ring A, L³, L⁴, R¹, R², R⁴, R⁵, and R^(G) are defined the same as the definition herein (e.g., any one of items 19 to 23 and 29 to 32, 103, 104, B18 to B22, B28 to B31, B91, B92, etc.).

A specific example of another embodiment of the compound of the invention includes a compound represented by formula (14):

or a pharmaceutically acceptable salt thereof. In formula (14), X, L³, L⁴, m, n, R⁵, and R^(G) are defined the same as the definition herein (e.g., any one of items 33 to 65, 103, 104, B32 to B59, B91, B92, etc.).

A specific example of another embodiment of the compound of the invention includes a compound represented by formula (15):

or formula (16):

or a pharmaceutically acceptable salt thereof. In formula (15) or formula (16), X, L³, L⁴, m, n, R⁵, and R^(G) are defined the same as the definition herein (e.g., any one of items 33 to 65, 103, 104, B32 to B59, B91, item B92, etc.).

The compound of the invention is described further hereinafter.

The compound of the invention can have, depending on the type of substituent, a tautomer, stereoisomers such as geometric isomer, and enantiomer, which are encompassed by the present invention. Specifically, if the compound of the invention has one or more asymmetric carbon atoms, there is a diastereomer or an enantiomer, where a mixture of such a diastereomer or enantiomer or isolated diastereomer or enantiomer are also encompassed by the compound of the invention. Accordingly, a description of a structure of the compound of the invention herein is interpreted as encompassing all possible isomers, unless specifically noted otherwise. For example with regard to tautomers, a description of one of two descriptions of the following imidazole groups, when either one is described, is interpreted as encompassing both tautomers and mixtures of any ratio of the tautomers in the compound of the invention.

For example with regard to asymmetric carbon atoms, if the structure of a bond with a substituent is described with a solid line (see, for example, the following description examples) or this is described only by a formula without an explicit description of isomers (e.g., —CH(NH₂)—, —CMe(NH₂)—, or the like), possible diastereomers, enantiomers, and other isomers are interpreted so that even if an individual isomer is explicitly described separately herein, regardless of the description, a mixture of such isomers of any ratio and each of any isolated possible isomer are encompassed by the compound of the invention by the description of the structure with a solid line or a description with only a formula.

The compound of the invention can also have a structure represented by the following formula (11) due to an equilibrium state or the like, depending on the environment conditions such as temperature or humidity, or a physical factor in a solid, liquid, solution, or the like. The compound of the invention also encompasses compounds with such a structure.

In formula (11), X represents a hydroxyl group, a thiol group, or —NHR^(a1), R^(G), R¹, R², R³, R⁴, R^(a1), R⁶¹, R⁶², R⁶³, and R⁶⁴ are defined the same as the definitions herein, and formula (1a) is defined the same as the definition herein.

For example, the structures of the compounds in the Examples herein are based on estimation considered the most appropriate by those skilled in the art using proton nuclear magnetic resonance spectrum (¹H-NMR), liquid chromatography mass spectrometry (LCMS), or the like, but the structures are just estimates under each specific measurement environment. In particular, the structure of formula (1a), the structure of formula (1b), and the structure of formula (11) are possibly converted to each other or partially converted to one of the structures and mixed due to a property unique to each compound, various environmental conditions such as temperature or humidity, or physical factor in a solid, liquid, solution or the like.

The compound of the invention also includes various hydrates, solvates, and crystalline polymorphisms.

Furthermore, the compound of the invention may be substituted with an isotope (e.g., ²H (or D), ³H (or T), ¹¹C, ¹³C, ¹⁴C, ¹³N, ¹⁵N, ¹⁵O, ³⁵S, ¹⁸F, ¹²⁵I, or the like). Such compounds are also encompassed by the compound of the invention.

Prodrugs of the compound of the invention are also within the scope of the invention. As used herein, a prodrug refers to a derivative that results in the compound of formula (1a), (1b), or (11) by acid hydrolysis or enzymatic degradation in the body. If, for example, the compound of formula (1a), (1b), or (11) has a hydroxyl group, amino group, or carboxyl group, these groups can be modified in accordance with a conventional method to manufacture a prodrug.

Examples for a compound with a carboxy group include compounds whose carboxyl group has been converted to an alkoxycarbonyl group, alkylthiocarbonyl group, or alkylaminocarbonyl group.

Examples for a compound with an amino group include compounds whose amino group has been substituted with an alkanoyl group to be converted to an alkanoylamino group, substituted with an alkoxycarbonyl group to be converted to an alkoxycarbonylamino group, modified to an alkanoyloxymethylamino group, or converted to a hydroxylamine.

Examples for a compound with a hydroxyl group include compounds whose hydroxyl group has been substituted with the alkanoyl group described above to be converted to an alkanoyloxy group, converted to a phosphate ester, or converted to an alkanoyloxymethyloxy group.

Examples of the alkyl moiety of a group used in producing prodrugs include the alkyl group described above. The alkyl group is optionally substituted with, for example, an alkoxy group or the like. Preferred examples thereof include the following.

Examples of compounds whose carboxyl group has been converted to an alkoxycarbonyl group include alkoxycarbonyl such as methoxycarbonyl and ethoxycarbonyl, and alkoxycarbonyl substituted with an alkoxy group such as methoxymethoxycarbonyl, ethoxymethoxycarbonyl, 2-methoxyethoxycarbonyl, 2-methoxyethoxymethoxycarbonyl, and pivaloyloxymethoxycarbonyl.

As used herein, “pharmaceutically acceptable salt” refers to an acid addition salt or base addition salt which is pharmaceutically acceptable for use. Examples of “pharmaceutically acceptable salts” include, but are not limited to, acid addition salts such as acetate, propionate, butyrate, formate, trifluoroacetate, maleate, fumarate, tartrate, citrate, stearate, succinate, ethylsuccinate, malonate, lactobionate, gluconate, glucoheptonate, benzoate, methanesulfonate, benzenesulfonate, para-toluenesulfonate (tosylate), laurylsulfate, malate, ascorbate, mandelate, saccharinate, xinafoate, pamoate, cinnamate, adipate, cysteine salt, N-acetyl cysteine salt, hydrochloride, hydrobromide, phosphate, sulfate, hydroiodide, nicotinate, oxalate, picrate, thiocyanate, undecanoate, acrylic acid polymer salt, and carboxyvinyl polymer; inorganic base addition salts such as lithium salt, sodium salt, potassium salt, and calcium salt; organic base addition salts such as morpholine and piperidine; amino acid addition salts wherein the amino acid is aspartic acid or glutamic acid; and the like.

The compounds of the invention can be administered directly, or as a formulation, medicament, or a pharmaceutical composition using a suitable dosage form, by oral or parenteral administration. Specific examples of such dosage forms include, but are not limited to, tablets, capsules, powder, granules, liquid agents, suspension, injections, patches, poultice, and the like. These formulations can be manufactured by a known method using an additive that is commonly used as a pharmaceutical additive.

As these additives, an excipient, disintegrant, binding agent, fluidizer, lubricant, coating agent, solubilizing agent, solubilization promotor, thickener, dispersant, stabilizer, sweetener, flavoring agent, or the like can be used depending on the objective. Specific examples of these additives include, but are not limited to, lactose, mannitol, crystalline cellulose, low-substituted hydroxypropyl cellulose, corn starch, partially pregelatinized starch, carmellose calcium, croscarmellose sodium, hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyvinyl alcohol, magnesium stearate, sodium stearyl fumarate, polyethylene glycol, propylene glycol, titanium oxide, talc, and the like.

The dosage of the compound of the invention is appropriately selected depending on the animal targeted for administration, route of administration, disease, patient's age, body weight, and symptom. For example, the dosage is 0.01 mg as the lower limit (preferably 100 mg) and 10000 mg as the upper limit (preferably 6000 mg) per day for adults for oral administration. This amount can be administered once daily, or divided into several doses.

The compound of the invention is a compound with inhibitory activity against β-lactamase. Thus, the compound can be a prophylactic or therapeutic agent that is useful for a bacterial infection by combined use with an antimicrobial agent. Specific examples of such bacterial infections include sepsis, febrile neutropenia, bacterial meningitis, bacterial endocarditis, otitis media, sinusitis, pneumonia, lung abscess, empyema, secondary infection of a chronic respiratory disease, pharyngolaryngitis, tonsillitis, osteomyelitis, arthritis, peritonitis, intraperitoneal abscess, cholecystitis, cholangitis, liver abscess, a deep skin infection, lymphangitis/lymphadenitis, secondary infection of trauma, burn injury, surgical wound, or the like, a urinary tract infection, a genital infection, an eye infection, an odontogenic infection, and the like.

The compound of the invention can be used in combination with at least one agent selected from an antimicrobial agent, an antifungal agent, an antiviral agent, an anti-inflammatory agent, or an anti-allergic agent for treating one or more bacterial infections described herein. The agent is preferably an antimicrobial agent, and more preferably a β-lactam agent. Specific examples thereof include amoxicillin, ampicillin (pivampicillin, hetacillin, bacampicillin, metampicillin, and talampicillin), epicillin, carbenicillin (carindacillin), ticarcillin, temocillin, azlocillin, piperacillin, mezlocillin, mecillinam (pivmecillinam), sulbenicillin, benzylpenicillin (G), clometocillin, benzathine benzylpenicillin, procaine benzylpenicillin, azidocillin, penamecillin, phenoxymethyl penicillin (V), propicillin, benzathine phenoxymethylpenicillin, phenethicillin, cloxacillin (dicloxacillin and flucloxacillin), oxacillin, methicillin, nafcillin, faropenem, biapenem, doripenem, ertapenem, imipenem, meropenem, panipenem, tomopenem, razupenem, cefazolin, cefacetrile, cefadroxil, cephalexin, cefaloglycin, cefalonium, cefaloridine, cephalothin, cephapirin, cefatrizine, cefazedone, cefazaflur, cefradine, cefroxadine, ceftezole, cefaclor, cefamandole, cefminox, cefonicide, ceforanide, cefotiam, cefprozil, cefbuperazone, cefuroxime, cefuzonam, cefoxitin, cefotetan, cefmetazole, loracarbef, cefixime, ceftazidime, ceftriaxone, cefcapene, cefdaloxime, cefdinir, cefditoren, cefetamet, cefmenoxime, cefodizime, cefoperazone, cefotaxime, cefpimizole, cefpiramide, cefpodoxime, cefsulodin, cefteram, ceftibuten, ceftiolene, ceftizoxime, flomoxef, latamoxef, cefepime, cefozopran, cefpirome, cefquinome, ceftobiprole, ceftaroline, CXA-101, RWJ-54428, MC-04546, ME1036, BAL30072, SYN2416, ceftiofur, cefquinome, cefovecin, aztreonam, tigemonam, carumonam, RWJ-442831, RWJ-333441, and RWJ-333442. The timing of dosing of the compound of the invention and therapeutic agents thereof is not limited. The compound and therapeutic agent can be administered concurrently or sequentially to a subject being administered therewith. The compound of the invention and the therapeutic agents can be formulated as a combined agent. The dosage of the therapeutic agent can be appropriately selected based on the clinically used dose. The ratio of the compound of the invention and the therapeutic agents can be appropriately selected depending on the subject of administration, route of administration, target disease, symptom, combination, or the like.

In another embodiment of the invention, the compound of the invention can be combined and administered concomitantly or administered at different times upon use of a pharmaceutical composition comprising an antimicrobial agent such as a β-lactam agent. Such a pharmaceutical composition comprising a β-lactam agent is also within the scope of the invention, and can be used for treating or preventing a bacterial infection such as sepsis, febrile neutropenia, bacterial meningitis, bacterial endocarditis, otitis media, sinusitis, pneumonia, lung abscess, empyema, secondary infection of a chronic respiratory disease, pharyngolaryngitis, tonsillitis, osteomyelitis, arthritis, peritonitis, intraperitoneal abscess, cholecystitis, cholangitis, liver abscess, a deep skin infection, lymphangitis/lymphadenitis, secondary infection of trauma, burn injury, surgical wound, or the like, a urinary tract infection, a genital infection, an eye infection, or an odontogenic infection.

Such a medicament, formulation, or pharmaceutical composition can be manufactured by mixing the compound of the invention and/or an additional agent (e.g., antimicrobial agent such as a β-lactam agent) with any suitable component, together or separately, as a combined agent or as separate agents using any technology that is known in the art. An appropriate formulation such as a tablet, capsule, powder, granule, liquid agent, suspension, injection, patch, or poultice can be formulated by using any technology that is known in the art. If the compound of the invention and/or an additional agent (e.g., antimicrobial agent such as a β-lactam agent) are prepared as separate agents, they can be provided as a kit of two agents. The kit can provide one of the components as a single agent, with instructions (package insert or the like) instructing to combine and administer the other component (for the compound of the invention, the additional agent (e.g., antimicrobial agent such as a β-lactam agent); for the addition agent (e.g., antimicrobial agent such as a β-lactam agent), the compound of the invention) concurrently or at different times.

If the compound of the invention is used as an active ingredient of a medicament, the compound can be intended for use in not just humans, but also animals other than humans (cat, dog, cow, chicken, fish, and the like).

Hereinafter, the method of manufacturing the compound of the invention is described with examples, but the present invention is not limited thereto.

The compound of the invention can be manufactured by, for example, the manufacturing methods described below, but the methods are not limited to such methods. These manufacturing methods can be appropriately improved upon based on the expertise of those skilled in the art of organic synthetic chemistry. Salts of the compounds used as a starting material can be used in the manufacturing method described below, as long as the reaction is not affected.

In the manufacturing methods described below, even if use of a protecting group is not specifically described, a functional group other than those at the reaction point can be protected as needed and deprotected after the completion of a reaction or after a series of reactions to obtain a compound of interest if one of the functional groups other than those at the reaction point is altered under the reaction condition or if it is unsuitable for post-reaction processing. Common protecting groups described in the document (T. W. Greene and P. G. M. Wuts, “Protective Group in Organic Synthesis”, 3^(rd) Ed., John Wiley and Sons, Inc., New York (1999)) or the like can be used as the protecting groups used in these processes. A protecting group can be introduced or removed by a method that is commonly used in organic synthetic chemistry (e.g., method described in the aforementioned document or the like) or a method in accordance therewith.

The starting material and intermediate in the manufacturing methods described below can be purchased as a commercially available product or are available by synthesis in accordance with a method described in a known document or a known method from a known compound. Salts of the starting material and intermediate can also be used, as long as the reaction is not affected.

The intermediate and compound of interest in the manufacturing methods described below can also be converted into another compound encompassed by the present invention by appropriately converting their functional groups. A functional group can be converted, in doing so, by a method that is commonly used in organic synthetic chemistry (e.g., the method described in R. C. Larock, “Comprehensive Organic Transformations”, 2^(nd) Ed., John Wiley and Sons, Inc., New York (1999) or the like) or a method in accordance therewith.

An inert solvent in the manufacturing methods described below refers to a solvent that does not react with starting materials, reagents, bases, acids, catalysts, ligands, or the like used in a reaction (hereinafter, also referred to as “starting materials or the like used in a reaction”). A solvent used in each step can be used as an inert solvent even if the solvent reacts with the starting materials or the like used in the reaction, as long as the reaction of interest proceeds to result in a compound of interest.

Manufacturing Method 1

Compound (1a-1), which is a compound represented by formula (1a) (hereinafter, also referred to as compound (1a); the same applies to other compounds) wherein G=O, can be manufactured, for example, by the following manufacturing method. The compound (1a) defined in item 1 can also be manufactured in the same manner.

wherein X, R¹, R², R³, R⁴, R⁶¹, R⁶², R⁶³, and R⁶⁴ are defined the same as item 1, PG¹ represents a protecting group of a hydroxyl group (e.g., a tert-butoxycarbonyl group, acetyl group, methoxymethyl group, p-methoxybenzyl group, tert-butyldimethylsilyl group, trimethylsilyl group, or the like), X^(a) is OPG³ or defined the same as X defined in item 1, and PG² and PG³ represent protecting groups of boronic acid (e.g., an optionally substituted C₁₋₆ alkyl group, a structure represented by the following formula formed together by PG² and PG³ as —B(OPG²)(OPG³), or the like).

Step 1-1: In this reaction step, compound (1a-1) can be manufactured in accordance with a known method (e.g., WO 2014/151958, WO 2015/191907, WO 2016/003929, WO 2018/005662, etc.) by using the compound represented by formula (II) (hereinafter, also referred to as compound (II)) as a raw material. More specifically, the compound can be manufactured, for example, by using step 1-1-1 or step 1-1-2 described below. Compound (II) can be manufactured, for example, in the same manner as Manufacturing Methods 4, 8, 15-19, or the like described below or a known method from a corresponding raw material that can be purchased or prepared.

Step 1-1-1: Compound (1a-1) can be manufactured by reacting boronic acid with compound (II) in an inert solvent under an acidic condition. Examples of boronic acid include phenylboronic acid and 2-methylpropyl boronic acid. The boronic acid can be used in the range of 0.001 to 100 equivalents with respect to compound (II), which is preferably 1 to 3 equivalents. Examples of acids include hydrochloric acid, trifluoroacetic acid, and the like. An acid can be used in the range of 0.001 to 100 equivalents with respect to compound (II), which is preferably 1 to 20 equivalents. Specific examples of inert solvents include halogenated hydrocarbon solvents such as dichloromethane and dichloroethane, hydrocarbon solvents such as hexane and heptane, ether solvents such as tetrahydrofuran (THF) and cyclopentyl methyl ether (CPME), nitrile solvents such as acetonitrile and propionitrile, acetic acid, and water, which can be used alone or as a mixture solvent. The acids described above can also be directly used as a solvent. A mixture solvent of hexane/acetonitrile, acetic acid, or CPME is preferably used as a solvent. The reaction temperature is selected from the range of about −10° C. to about 100° C., but is more preferably in the range of about 0° C. to room temperature.

Step 1-1-2: compound (1a-1) can be manufactured by reacting triethylsilane with compound (II) in a trifluoroacetic acid solvent. The triethylsilane can be used in the range of 0.001 to 100 equivalents with respect to compound (II), which is preferably 1 to 50 equivalents. The reaction temperature is selected from the range of about −10° C. to about 70° C.

Manufacturing Method 2

Compound (1a-2), which is compound (1a-1) wherein R⁶¹, R⁶², R⁶³ and R⁶⁴ are hydrogen atoms, can be manufactured, for example, by the manufacturing method described below.

wherein X, R¹, R², R³, and R⁴ are defined the same as item 1.

Step 2-1: In this reaction step, compound (1a-2) can be manufactured in accordance with a known method (e.g., WO 2019/075084, etc.) by using a corresponding compound (III) as a raw material. Compound (III) can be manufactured, for example, in the same manner as Manufacturing Methods 12, 13, 23, or 24 described below or a known method from a corresponding raw material that can be purchased or prepared.

More specifically, compound (1a-2) can be manufactured, for example, by reacting metal carbenoid or halogenated organic zinc with compound (III) in an inert solvent. Examples of metal carbenoid include diazomethane/palladium (II) acetate (wherein (II) indicates that palladium is divalent). The diazomethane can be used in the range of 1 to 100 equivalents with respect to compound (III), which is preferably 1 to 3 equivalents. The palladium (II) acetate can be used in the range of 0.001 to 10 equivalents with respect to compound (III), which is preferably 0.01 to 1 equivalent. Examples of halogenated organic zinc include diiodomethane/diethylzinc. The diiodomethane can be used in the range of 1 to 100 equivalents with respect to compound (III), which is preferably 1 to 20 equivalents. The diethylzinc can be used in the range of 1 to 100 equivalents with respect to compound (III), which is preferably 1 to 10 equivalents. Specific examples of inert solvents include halogenated hydrocarbon solvents such as dichloromethane and dichloroethane, ether solvents such as THF and 1,2-dimethoxyethane (DME), which can be used alone or as a mixture solvent. The reaction temperature is selected from the range of about −100° C. to the boiling point of the solvent used, but is more preferably in the range of about −78° C. to room temperature.

Manufacturing Method 3

Compound (1a-1) can be obtained as compound (1b-1), which is a compound represented by formula (1b) wherein G=O, by, for example, reacting with a reagent that generates nucleophilic X⁻ (X anion) (e.g., alkali metal salt generating a hydroxide anion HO, alkali metal salt of C₁₋₆ alkoxide generating a C₁₋₆ alkoxide anion, the alkali metal salt of amide generating amide anion R^(a2)R^(b1)N⁻, or the like), depending on the property of compound. Compound (1b) defined in item 1 can be manufactured in the same manner.

wherein X, R¹, R², R³, R⁴, R⁶¹, R⁶², R⁶³, and R⁶⁴ are defined the same as item 1.

For example, a compound of formula (1a-3), which is a compound represented by formula (1a-1) wherein X is a hydroxyl group, can be treated with an alkali aqueous solution to obtain a compound of formula (1b-3) as an alkali metal salt. As an alkali aqueous solution, an aqueous solution of the alkali metal salt generating a hydroxide anion HO described above (e.g., potassium carbonate, sodium carbonate, potassium hydrogen carbonate, sodium hydrogen carbonate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, potassium phosphate, sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium phosphate, potassium hydroxide, sodium hydroxide, or the like) can be used. More specifically, for example, compound (1a-3) can be treated with an aqueous sodium hydroxide solution to obtain a compound of formula (1b-3) as a sodium salt depending on the property of compound. Compound (1a-3) can be treated with an alkali aqueous solution upon purification or post-processing after a manufacturing reaction to be isolated as compound (1b-3), or converted into compound (1b-3) by applying said treatment on the isolated compound (1a-3).

wherein R¹, R², R³, R⁴, R⁶¹, R⁶², R⁶³, and R⁶⁴ are defined the same as item 1.

For example, a compound of formula (1a-4), which is a compound represented by formula (1a-1) wherein X is a hydroxyl group and R⁴ is a carboxyl group, can be obtained as a disodium salt compound of formula (1b-4) by treatment with an aqueous sodium hydroxide solution depending on the property of the compound.

wherein R¹, R², R³, R⁶¹, R⁶², R⁶³, and R⁶⁴ are defined the same as item 1. In formula (1b-4), two sodium ions Na⁺ are described separately in the vicinity of two types of negatively charged groups, but this is synonymous to describing collectively as 2Na⁺ and represents disodium salt.

For example, a compound of formula (5a-1), which is a compound represented by formula (5a) defined in item 24 wherein R³ is a carboxyl group, is obtained in some cases as a trisodium salt compound of formula (5b-1), depending on the property of the compound, by treatment with an aqueous sodium hydroxide solution.

wherein A, L³, L⁴, Y, R¹, and R² are defined the same as any one of items 1 to 24. In formula (5b-1), three sodium ions Na⁺ are described separately in the vicinity of three types of negatively charged groups, but this is synonymous to describing collectively as 3Na⁺ and represents trisodium salt.

Manufacturing Method 4

Compound (II), which is represented by formula (II-1) described below can be manufactured, for example, by the manufacturing method described below.

wherein Y, A, L³, L⁴, R¹, R², R⁴, and R⁵ are defined the same as item 1. PG⁴ represents a protecting group of a hydroxyl group (e.g., tert-butoxycarbonyl group, acetyl group, methoxymethyl group, p-methoxybenzyl group, tert-butyldimethylsilyl group, trimethylsilyl group, methyl group, or the like). In formula (VI), H in group —Y—H is a hydrogen atom, T represents a hydroxyl group or a leaving group (e.g., a halogen atom such as chlorine, bromine, or iodine, a lower alkylsulfonyloxy group such as methane sulfonyloxy, a trihalogenomethanesulfonyloxy group such as trifluoromethanesulfonyloxy, an arylsulfonyloxy group such as benzenesulfonyloxy or p-toluenesulfonyloxy, or the like), and PG¹, PG², and PG³ are each defined the same as the definition described in Manufacturing Method 1.

Step 4-1: Compound (V) can be manufactured by a method according to step 2-1 of Manufacturing Method 2 by using compound (IV) as a raw material. Compound (IV) can be manufactured, for example, in the same manner as Manufacturing Methods 5 to 7 described below or a known method from a corresponding raw material that can be purchased or prepared.

Step 4-2: Compound (VI) can be manufactured by deprotecting protecting group PG⁴ of compound (V). This step can be performed, for example, in accordance with the method described in a reference (T. W. Greene and P. G. M. Wuts, “Protective Group in Organic Synthesis”, 3^(rd) Ed., John Wiley and Sons, Inc., New York (1999) or the like).

Step 4-3: If Y is an oxygen atom, and T is a hydroxyl group, compound (II) can be manufactured by reacting compound (VII) with compound (VI) under the so-called Mitsunobu reaction in an inert solvent in the presence of an azo compound analog and an organic phosphorous compound or phosphorane compound under normal pressure or under pressure. Specific examples of inert solvents include ether solvents such as THF and DME, hydrocarbon solvents such as toluene and benzene, and the like. Examples of azo compound analogs include diethyl azodicarboxylate, diisopropyl azodicarboxylate, and the like. An azo compound analog can be used at 0.001 to 100 equivalents with respect to compound (VI), which is preferably 1 to 10 equivalents. Examples of organic phosphorous compounds include triphenylphosphine, tributylphosphine, and the like. An organic phosphorous compound can be used at 0.001 to 100 equivalents with respect to compound (VI), which is preferably 1 to 10 equivalents. Examples of phosphorane compounds include (cyanomethylene)tributylphosphorane, (cyanomethylene)trimethylphosphorane, and the like. A phosphorane compound can be used at 0.001 to 100 equivalents with respect to compound (VI), which is preferably 1 to 10 equivalents. The reaction temperature is selected from the range of about −10° C. to about 100° C.

Alternatively, if Y is an oxygen atom, a sulfur atom, or —NR^(j)—, and T is a leaving group (e.g., a halogen atom such as chlorine, bromine, or iodine, a lower alkylsulfonyloxy group such as a methanesulfonyloxy group, a trihalogenomethanesulfonyloxy group such as a trifluoromethanesulfonyloxy group, an arylsulfonyloxy group such as a benzenesulfonyloxy group or p-toluenesulfonyloxy group, or the like), compound (II) can be manufactured by reacting compound (VII) with compound (VI) in an inert solvent in the presence of a base under normal pressure or under pressure. Specific examples of inert solvents include ether solvents such as THF and DME, halogenated hydrocarbon solvents such as dichloromethane and dichloroethane, aprotic solvents such as N,N-dimethylformamide (DMF), N-methylpyrrolidone (NMP), and dimethyl sulfoxide (DMSO), and the like. Examples of bases include potassium tert-butoxy, sodium hydride, triethylamine, diisopropylethylamine, potassium carbonate, sodium carbonate, cesium carbonate, and the like. A base can be used at 0.001 to 100 equivalents with respect to compound (VI), which is preferably 0.5 to 10 equivalents. Compound (VII) can be used at 0.001 to 100 equivalents with respect to compound (VI), which is preferably 1 to 10 equivalents. The reaction temperature is selected from the range of about −10° C. to about 100° C.

Manufacturing Method 5

Compound (IV) can be manufactured, for example, by the manufacturing method described below by using compound (VIII) as a raw material.

wherein Y, R¹, R², and R⁴ are defined the same as item 1. X¹ represents an iodine atom, a bromine atom, a chlorine atom, or a substituted sulfonyloxy group (e.g., methanesulfonyloxy group, trifluoromethanesulfonyloxy group, p-toluenesulfonyloxy group, or the like), PG¹, PG², and PG³ are each defined the same as the definition described in Manufacturing Method 1, and PG⁴ is defined the same as the definition described in Manufacturing Method 4.

A commercially available product that is purchased or a compound synthesized in accordance with a known method (e.g., the method described in R. C. Larock, “Comprehensive Organic Transformations”, 2^(nd) Ed., John Wiley and Sons, Inc., New York (1999), or the method described in WO 2016/003929, WO 2016/149393, or the like) from a known compound as the starting material compound (VIII).

Step 5-1: Compound (IX) can be manufactured by a coupling reaction of vinyl boronate ester with compound (VIII) in an inert solvent in the presence of a transition metal catalyst and a base under a so-called Heck reaction condition. The reaction may be performed in the presence of a ligand as needed. Specific examples of vinyl boronate ester include 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborolane. The vinyl boronate ester can be used in the range of 1 to 100 equivalents with respect to compound (VIII), which is preferably 1 to 3 equivalents. Specific examples of transition metal catalysts include palladium (II) acetate, tris(dibenzylideneacetone)dipalladium(0), and bis(tri-tert-butylphosphine)palladium(0) (wherein (II) and (0) indicate that palladium is divalent and zerovalent, respectively). The transition metal catalyst can be used in the range of 0.001 to 10 equivalents with respect to compound (VIII), which is preferably 0.01 to 1 equivalent. Specific examples of bases include organic bases such as triethylamine and inorganic bases such as potassium carbonate, silver carbonate, and potassium acetate. The base can be used in the range of 1 to 100 equivalents with respect to compound (VIII), which is preferably 1 to 5 equivalents. Specific examples of ligands include BINAP and tri(o-tolyl)phosphine. The ligand can be used in the range of 0.001 to 10 equivalents with respect to compound (VIII), which is preferably 0.01 to 2 equivalents. Specific examples of inert solvents include halogenated hydrocarbon solvents such as dichloromethane and dichloroethane, ether solvents such as THF and CPME, aromatic hydrocarbon solvents such as toluene and benzene, and aprotic polar solvents such as DMF and N,N-dimethylacetamide (DMA), which can be used alone or as a mixture solvent. Toluene is preferably used as a solvent. The reaction temperature is selected from the range of room temperature to the boiling point of the solvent used, but is more preferably in the range of about 50° C. to about 130° C.

Step 5-2: Compound (IV) can be manufactured from corresponding compound (IX) in accordance with a known method (e.g., Angewandte Chemie International Edition (2018), 57(XII), 3168-3172).

More specifically, compound (IV) is a compound in which a geometric isomerism of a double bond is a (Z) form (or cis form). This compound can be manufactured through an EZ isomerization reaction by light irradiation on compound (IX) obtained primarily as an (E) form (or trans form) in the previous step in the presence of a photoreaction catalyst (photosensitizer) in an inert solvent. Specific examples of photoreaction catalysts include tris(2-phenylpyridinato)iridium(III). The photoreaction catalyst can be used in the range of 0.001 to 10 equivalents with respect to compound (IX), which is preferably 0.01 to 2 equivalents. Preferred examples of wavelengths of irradiated light include 450 nm. Specific examples of inert solvents include acetonitrile. The reaction temperature is selected from the range of about −10° C. to the boiling point of the solvent used, but is more preferably in the range of about 0° C. to about 50° C.

Manufacturing Method 6

Compound (IV) can be manufactured, for example, by the manufacturing method described below by using compound (VIII) as a raw material. Compound (IV) can also be manufactured from compound (VIII) in accordance with a known method (e.g., WO 2018/005662, etc.).

wherein Y, R¹, R², and R⁴ are defined the same as item 1. PG⁵ is a protecting group of terminal alkyne (trimethylsilyl group, tert-butyldimethylsilyl group, or the like), X¹ is defined the same as the definition described in Manufacturing Method 5, PG¹, PG², and PG³ are each defined the same as the definition described in Manufacturing Method 1, and PG⁴ is defined the same as the definition described in Manufacturing Method 4.

Step 6-1: Compound (X) can be manufactured through a coupling reaction of a terminal alkyne compound with only one end of acetylene protected by PG⁵ with compound (VIII) in an inert solvent in the presence of a transition metal catalyst, copper catalyst, and base under a so-called Sonogashira reaction condition. The reaction can be performed in the presence of a ligand as needed. Specific examples of terminal alkyne compounds include trimethylsilylacetylene and (tert-butyldimethylsilyl)acetylene. The terminal alkyne compound can be used in the range of 1 to 100 equivalents with respect to compound (VIII), which is preferably 1 to 3 equivalents. Specific examples of transition metal catalysts include tetrakis(triphenylphosphine)palladium(0), dichlorobis(triphenylphosphine)palladium(II), dichlorobis(acetonitrile)palladium(II), and palladium(II) chloride (wherein (0) and (II) indicate that palladium is zerovalent and divalent, respectively). The transition metal catalyst can be used in the range of 0.001 to 10 equivalents with respect to compound (VIII), which is preferably 0.01 to 1 equivalent. Specific examples of copper catalysts include copper powder, halogenated copper (I), copper (I) acetate, and the like, and preferred examples include copper (I) iodide (wherein (I) indicates that copper is monovalent). The copper catalyst can be used in the range of 0.001 to 10 equivalents with respect to compound (VIII), which is preferably 0.01 to 1 equivalent. Specific examples of bases include diethylamine, triethylamine, and the like. The base can be used in the range of 1 to 100 equivalents with respect to compound (VIII), which is preferably 1 to 5 equivalents. Specific examples of ligands include triphenylphosphine, tri-tert-butylphosphine, 2,2-bis(diphenylphosphino)-1,1-binaphthyl, 2-(di-tert-butylphosphino)biphenyl, 1,1′-bis(diphenylphosphino)ferrocene, and the like. The ligand can be used in the range of 0.001 to 10 equivalents with respect to compound (VIII), which is preferably 0.01 to 2 equivalents. Specific examples of inert solvents include ether solvents such as tetrahydrofuran (THF) and diethyl ether, and aprotic polar solvents such as N,N-dimethylformamide (DMF), which can be used alone or as a mixture solvent. Toluene is preferably used as a solvent. The reaction temperature is selected from the range of about −78° C. to the boiling point of the solvent used.

Step 6-2: Compound (XI) can be manufactured by removing protecting group PG⁵ of compound (X) from using a known deprotecting reaction (see, for example, T. W. Greene and P. G. M. Wuts, “Protective Group in Organic Synthesis”, 3^(rd) Ed., John Wiley and Sons, Inc., New York (1999)).

Step 6-3: Compound (IV) can be manufactured from a corresponding compound (XI) in accordance with a known method (e.g., Journal of the American Chemical Society (2000), 122(XX), 4990-4991).

Step 6-4: Compound (XII) can be manufactured from a corresponding compound (XI) in accordance with a known method (e.g., Chemical Science (2017), 8(1), 165-168).

Step 6-5: Compound (IV) can be manufactured by catalytic hydrogenation on compound (XII) in an inert solvent in the presence of a catalyst and under a hydrogen atmosphere. Specific examples of catalysts include a Lindlar's catalyst. The catalyst can be used in the range of 0.005 to 50 equivalents with respect to compound (XII), which is preferably 0.01 to 10 equivalents. Specific examples of inert solvents include ester solvents such as ethyl acetate and alcohol solvents such as methanol and ethanol, which can be used alone or as a mixture solvent. The reaction temperature is selected from the range of about −20° C. to the boiling point of the solvent used, but is more preferably in the range of about 0° C. to about 50° C. Hydrogen pressure is generally normal pressure, but can be adjusted to medium or high pressure in accordance with the reactivity of a compound.

Manufacturing Method 7

Compound (IV) can be manufactured, for example, by the manufacturing method described below by using compound (VIII) as a raw material.

wherein Y, R¹, R², and R⁴ are defined the same as item 1. X² is an iodine atom, a bromine atom, a chlorine atom, or a substituted sulfonyloxy group (e.g., a methanesulfonyloxy group or a trifluoromethanesulfonyloxy group), X¹ is defined the same as the definition described in Manufacturing Method 5, PG¹, PG², and PG³ are each defined the same as the definition described in Manufacturing Method 1, and PG⁴ is defined the same as the definition described in Manufacturing Method 4.

Step 7-1: Compound (XIII) can be manufactured from a corresponding compound (VIII) in accordance with a known method (e.g., WO 2018/005662, WO 2019/075084, etc.).

Step 7-2: Compound (IV) can be manufactured by a coupling reaction of compound (XIII) with a corresponding borane compound in an inert solvent in the presence of a transition metal catalyst and a base under a so-called Miyaura-Ishiyama borylation reaction condition. The reaction can be performed in the presence of a ligand as needed. Specific examples of borane compounds include pinacolborane, pinacoldiborane, and diboronic acid. A borane compound can be used in the range of 1 to 100 equivalents with respect to compound (XIII), which is preferably 1 to 3 equivalents. Specific examples of transition metal catalysts include [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloride, tris(dibenzylideneacetone)palladium(0), and the like (wherein (II) and (0) indicate that palladium is divalent and zerovalent, respectively). An transition metal catalyst can be used in the range of 0.001 to 10 equivalents with respect to compound (XIII), which is preferably 0.01 to 1 equivalents. Specific examples of ligands include triphenylphosphine, XPhos, 2-(di-tert-butylphosphino)biphenyl, 1,1′-bis(diphenylphosphino)ferrocene, and the like. A ligand can be used in the range of 0.001 to 10 equivalents with respect to compound (XIII), which is preferably 0.01 to 2 equivalents. Specific examples of bases include potassium acetate, potassium phenoxide, and the like. A base can be used in the range of 1 to 100 equivalents with respect to compound (XIII), which is preferably 1 to 5 equivalents. Specific examples of inert solvents include halogenated hydrocarbon solvents such as dichloromethane and dichloroethane, ether solvents such as THF and 1,4-dioxane, and aprotic polar solvents such as DMF and DMSO, which can be used alone or as a mixture solvent. The reaction temperature is selected from the range of about −20° C. to about 180° C., but is more preferably in the range of about 50° C. to about 130° C.

Manufacturing Method 8

Compound (II-1) can be manufactured, for example, by the manufacturing method described below by using compound (XIV) as a raw material.

wherein Y, A, L³, L⁴, R¹, R², R⁴, and R⁵ are defined the same as item 1. PG¹, PG², and PG³ are each defined the same as the definition described in Manufacturing Method 1.

Step 8-1: Compound (II) can be manufactured by the method in accordance with step 2-1 in Manufacturing Method 2 by using compound (XIV) as a raw material. Compound (XIV) can be manufactured, for example, in the same manner as Manufacturing Methods 9 to 11 described below or a known method from a corresponding raw material that can be purchased or prepared.

Manufacturing Method 9

Compound (XIV) can be manufactured, for example, by the manufacturing method described below by using compound (IV) as a raw material.

wherein Y, A, L³, L⁴, R¹, R², R⁴, and R⁵ are defined the same as item 1. PG¹, PG², and PG³ are each defined the same as the definition described in Manufacturing Method 1, and T and PG⁴ are defined the same as the definition described in Manufacturing Method 4.

Step 9-1: compound (XV) can be manufactured by a method in accordance with step 4-2 in Manufacturing Method 4 by using compound (IV) as a raw material.

Step 9-2: Compound (XIV) can be manufactured by a method in accordance with step 4-3 in Manufacturing Method 4 by using compound (XV) as a raw material.

Manufacturing Method 10

Compound (XIV) can also be manufactured, for example, by the manufacturing method described below by using compound (IX) as a raw material.

wherein Y, A, L³, L⁴, R¹, R², R⁴, and R⁵ are defined the same as item 1. PG¹, PG², and PG³ are each defined the same as the definition described in Manufacturing Method 1, H of group —Y—H in formula (XVI) is a hydrogen atom, and T and PG⁴ are defined the same as the definition described in Manufacturing Method 4.

Step 10-1: Compound (XVI) can be manufactured by a method in accordance with step 4-2 in Manufacturing Method 4 by using compound (IX) as a raw material.

Step 10-2: Compound (XVII) can be manufactured by a method in accordance with step 4-3 in Manufacturing Method 4 by using compound (XVI) as a raw material.

Step 10-3: Compound (XIV) can be manufactured by a method in accordance with step 5-2 in Manufacturing Method 5 by using compound (XVII) as a raw material.

Manufacturing Method 11

Compound (XIV) can also be manufactured, for example, by the manufacturing method described below by using compound (XII) as a raw material.

wherein Y, A, L³, L⁴, R¹, R², R⁴, and R⁵ are defined the same as item 1. PG¹, PG², and PG³ are each defined the same as the definition described in Manufacturing Method 1, H of group —Y—H in formula (XVIII) is a hydrogen atom, and T and PG⁴ are defined the same as the definition described in Manufacturing Method 4.

Step 11-1: Compound (XVIII) can be manufactured by a method in accordance with step 4-2 in Manufacturing Method 4 by using compound (XII) as a raw material.

Step 11-2: Compound (XIX) can be manufactured by a method in accordance with step 4-3 in Manufacturing Method 4 by using compound (XVIII) as a raw material.

Step 11-3: Compound (XIV) can be manufactured by a method in accordance with step 6-5 in Manufacturing Method 6 by using compound (XIX) as a raw material.

Manufacturing Method 12

Compound (III) represented by formula (III-1) can be manufactured, for example, by the manufacturing method described below by using compound (XIV) as a raw material.

wherein X, Y, A, L, L, R¹, R², R⁴, and R⁵ are defined the same as item 1. PG¹, PG², and PG³ are each defined the same as the definition described in Manufacturing Method 1.

Step 12-1: Compound (III-1) can be manufactured by a method in accordance with step 1-1, step 1-1-1, or step 1-1-2 in Manufacturing Method 1 by using compound (XIV) as a raw material.

Manufacturing Method 13

Compound (III-1) can also be manufactured, for example, by the manufacturing method described below by using compound (X) as a raw material.

wherein Y, A, L³, L⁴, R¹, R², R⁴, and R⁵ are defined the same as item 1. PG¹, PG², and PG³ are each defined the same as the definition described in Manufacturing Method 1, H of group —Y—H in formula (XX) is a hydrogen atom, T and PG⁴ are defined the same as the definition described in Manufacturing Method 4, and PG⁵ is defined the same as the definition described in Manufacturing Method 6.

Step 13-1: Compound (XX) can be manufactured by a method in accordance with step 4-2 in Manufacturing Method 4 by using compound (X) as a raw material.

Step 13-2: Compound (XXI) can be manufactured by a method in accordance with step 4-3 in Manufacturing Method 4 by using compound (XX) as a raw material.

Step 13-3: Compound (XXII) can be manufactured by a method in accordance with step 6-2 in Manufacturing Method 6 by using compound (XXI) as a raw material.

Step 13-4: Compound (XXIII) can be manufactured by a method in accordance with step 4-2 in Manufacturing Method 4 by using compound (XXII) as a raw material.

Step 13-5: Compound (XXIV) can be manufactured by an intramolecular cyclization reaction on compound (XXIII) in an inert solvent in the presence of a catalyst and a base. Specific examples of catalysts include copper iodide and the like. A catalyst can be used in the range of 0.001 to 10 equivalents with respect to compound (XXIII), which is preferably 0.01 to 1 equivalent. Specific examples of bases include triethylamine, sodium carbonate, and the like. A base can be used in the range of 1 to 200 equivalents with respect to compound (XXIII), which is preferably 1 to 50 equivalents. Specific examples of inert solvents include alcohol solvents such as ethanol and aprotic polar solvents such as DMF and DMSO, which can be used alone or as a mixture solvent. The reaction temperature is selected from the range of about 0° C. to about 180° C., but is more preferably in the range of about 50° C. to about 130° C.

Step 13-6: Compound (III-1) can be manufactured from a corresponding compound (XXIV) in accordance with a known method (e.g., Journal of the American Chemical Society (2016), 138 (47), 15315-15318, WO 2019/075084, etc.). More specifically, compound (III-1) can be manufactured by reacting diboron with compound (XXIV) in an inert solvent in the presence of a transition metal catalyst and a base. Examples of diboron include bis(pinacolato)diboron and bis(pinanediolato)diboron. Diboron can be used in the range of 1 to 100 equivalents with respect to compound (XXIV), which is preferably 1 to 3 equivalents. Examples of transition metal catalysts include [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene]triphenylphosphine nickel (II) dichloride and bis(1,5-cyclooctadiene) nickel(0)/1,3-dimethylimidazol-2-ylidene (wherein (II) and (0) indicate that nickel is divalent and zerovalent, respectively). A transition metal catalyst can be used in the range of 0.001 to 10 equivalents with respect to compound (XXIV), which is preferably 0.01 to 1 equivalent. Specific examples of bases include potassium carbonate and cesium carbonate, and cesium carbonate is preferably used. A base can be used in the range of 1 to 100 equivalents with respect to compound (XXIV), which is preferably 1 to 5 equivalents. Specific examples of inert solvents include halogenated hydrocarbon solvents such as dichloromethane and dichloroethane, ether solvents such as THF and CPME, and aromatic hydrocarbon such as toluene and benzene, which can be used alone or as a mixture solvent. Toluene is preferably used as an inert solvent. The reaction temperature is selected from the range of room temperature to the boiling point of the solvent used, but is more preferably in the range of about 80° C. to about 110° C.

Manufacturing Method 14

Compound (XXIV) can also be manufactured, for example, by the manufacturing method described below by using compound (X) as a raw material.

wherein Y, A, L³, L⁴, R¹, R², R⁴, and R⁵ are defined the same as item 1. PG¹, PG², and PG³ are each defined the same as the definition described in Manufacturing Method 1, H of group —Y—H in formula (XXVIII) is a hydrogen atom, T and PG⁴ are defined the same as the definition described in Manufacturing Method 4, and PG⁵ is defined the same as the definition described in Manufacturing Method 6.

Step 14-1: Compound (XXV) can be manufactured by a method in accordance with step 6-2 in Manufacturing Method 6 by using compound (X) as a raw material.

Step 14-2: Compound (XXVI) can be manufactured by a method in accordance with step 4-2 in Manufacturing Method 4 by using compound (XXV) as a raw material.

Step 14-3: Compound (XXVII) can be manufactured by a method in accordance with step 13-5 in Manufacturing Method 13 by using compound (XXVI) as a raw material.

Step 14-4: Compound (XXVIII) can be manufactured by a method in accordance with step 4-2 in Manufacturing Method 4 by using compound (XXVII) as a raw material.

Step 14-5: Compound (XXIV) can be manufactured by a method in accordance with step 4-3 in Manufacturing Method 4 by using compound (XXVIII) as a raw material.

Manufacturing Method 15

A compound represented by formula (II), which is represented by formula (II-2), can be manufactured, for example, by the manufacturing method described below by using compound (XXIX) as a raw material.

wherein Y, L³, L⁴, R¹, R², R⁴, and R⁵ are defined the same as item 1, and m and n are defined the same as item 33. PG¹, PG², and PG³ are each defined the same as the definition described in Manufacturing Method 1, PG⁶ is a protecting group of an amino group (e.g., an ethoxycarbonyl group, tert-butoxycarbonyl group, acetyl group, benzoyl group, trifluoroacetyl group, benzyloxycarbonyl group, 3- or 4-chlorobenzyloxycarbonyl group, triphenylmethyl group, methanesulfonyl group, p-toluenesulfonyl group, trimethylsilyl group, benzyloxycarbonyl group, 3- or 4-chlorobenzyloxycarbonyl group, benzylsulfonyl group, benzyl group, 4-nitrobenzyl group, 4-methoxybenzyl group, methyl group, ethyl group, or the like), and J is a leaving group (e.g., a halogen atom such as chlorine, bromine, or iodine, or a substituted sulfonyloxy group (e.g., a methanesulfonyloxy group, a trifluoromethanesulfonyloxy group, a p-toluenesulfonyloxy group, or the like)).

Step 15-1: Compound (XXX) can be manufactured by deprotecting protecting group PG⁶ of compound (XXIX). This step can be performed, for example, in accordance with a method described in a reference (T. W. Greene and P. G. M. Wuts, “Protective Group in Organic Synthesis”, 3^(rd) Ed., John Wiley and Sons, Inc., New York (1999)) or the like. Compound (XXIX) can be manufactured, for example, in the same manner as Manufacturing Method 18 or 19 described below or a known method from a corresponding raw material that can be purchased or prepared.

Step 15-2: Compound (II-2) can be manufactured by reacting compound (XXXI-1) in an inert solvent in the presence of a base by using compound (XXX) as a raw material. The reaction can be performed in the presence of a suitable phase transfer catalyst as needed. Compound (XXXI-1) can be used at 0.001 to 100 equivalents with respect to compound (XXX), which is preferably 1 to 10 equivalents.

Specific examples of bases include organic bases such as triethylamine, N,N-diisopropylethylamine, and pyridine, inorganic bases such as potassium carbonate, sodium carbonate, cesium carbonate, potassium hydrogen carbonate, sodium hydrogen carbonate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, potassium phosphate, sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium phosphate, potassium hydroxide, sodium hydroxide, and sodium hydride, and metal alkoxide such as sodium methoxide and potassium tert-butoxide. A base can be used at 0.001 to 100 equivalents with respect to compound (XXX), which is preferably 0.5 to 10 equivalents. Specific examples of phase transfer catalysts include tetrabutylammonium hydrogensulfate and the like. A phase transfer catalyst can be used at 0.001 to 100 equivalents with respect to compound (XXX), which is preferably 0.1 to 10 equivalents. Specific examples of inert solvents include halogenated hydrocarbons such as chloroform and dichloromethane, aromatic hydrocarbons such as benzene and toluene, ether solvents such as tetrahydrofuran (THF), diethyl ether, 1,4-dioxane, and 1,2-dimethoxyethane (DME), lower alcohol such as methanol, ethanol, and 2-propanol, aprotic polar solvents such as acetonitrile, N,N-dimethylformamide (DMF), and N-methyl-2-pyrrolidone (NMP), water, and mixture solvents thereof. The reaction temperature is selected from the range of about −20° C. to the boiling point of the solvent used.

Manufacturing Method 16

A compound of formula (II) represented by formula (II-3) can be manufactured, for example, by the manufacturing method described below by using compound (XXX) as a raw material.

wherein Y, L⁴, R¹, R², R⁴, and R⁵ are defined the same as item 1, and m and n are defined the same as item 33. PG¹, PG², and PG³ are each defined the same as the definition described in Manufacturing Method 1, and PG⁶ is defined the same as the definition described in Manufacturing Method 15.

Step 16-1: Compound (II-3) can be manufactured by a condensation reaction of compound (XXX) with compound (XXXI-2) in an inert solvent in the presence of a condensing agent. Compound (XXXI-2) can be used at 0.001 to 100 equivalents with respect to compound (XXX), which is preferably 1 to 10 equivalents. Various condensing agents that are used in a conventional method can be used as the condensing agent. Examples thereof include 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC, EDCI) (and hydrochlorides thereof), 0-(7-azabenzotriazol-1-yl)-N,N,N′,N′,-tetramethyluronium hexafluorophosphate (HATU), and the like. A condensing agent can be used at 0.001 to 100 equivalents with respect to compound (XXX), which is preferably 1 to 10 equivalents. Examples of bases include diisopropylethylamine, triethylamine, and the like. A base can be used at 0.001 to 100 equivalents with respect to compound (XXX), which is preferably 1 to 10 equivalents. Specific examples of inert solvents include ether solvents such as THF and DME, halogenated hydrocarbon solvents such as dichloromethane and chloroform, aprotic solvents such as DMF, NMP, and DMSO, and the like. The reaction temperature is selected from the range of about −78° C. to about 100° C.

Manufacturing Method 17

A compound of formula (II) represented by formula (II-4) can be manufactured, for example, by the manufacturing method described below by using compound (XXX) as a raw material,

wherein Y, L⁴, R¹, R², R⁴, and R⁵ are defined the same as item 1, and m and n are defined the same as item 33. PG¹, PG², and PG³ are each defined the same as the definition described in Manufacturing Method 1, PG⁶ is defined the same as the definition described in Manufacturing Method 15, and R⁶ represents a hydrogen atom or an optionally substituted C₁₋₆ alkyl group.

Step 17-1: Compound (II-4) can be manufactured by a so-called reductive amination reaction of compound (XXXI-3) with compound (XXX) in an inert solvent in the presence of a reducing agent. The reaction can be performed in the presence of a base, an acid, or other additives as needed. Compound (XXXI-3) can be used at 0.001 to 100 equivalents with respect to compound (XXX), which is preferably 1 to 10 equivalents. Specific examples of reducing agents include lithium aluminum hydride, sodium borohydride, sodium triacetoxyborohydride, sodium cyanoborohydride, diisobutylaluminium hydride, lithium tri(sec-butyl)borohydride, sodium tri(sec-butyl)borohydride, potassium tri(sec-butyl)borohydride, borane-dimethylsulfide complex, borane-tetrahydrofuran complex, lithium triethyl borohydride, ammonium formate, and the like. Alternatively, a hydrogenation reaction can also be performed using a metal catalyst such as palladium on carbon or palladium oxide instead of a reducing agent. A reducing agent can be used at 0.001 to 100 equivalents with respect to compound (XXX), which is preferably 0.5 to 10 equivalents. Specific examples of bases include organic bases such as triethylamine, diisopropylethylamine, and pyridine; inorganic bases such as potassium carbonate, sodium carbonate, cesium carbonate, potassium hydrogen carbonate, sodium hydrogen carbonate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, potassium phosphate, sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium phosphate, potassium hydroxide, sodium hydroxide, and sodium hydride; metal alkoxides such as sodium methoxide and potassium tert-butoxide; and the like. A base can be used at 0.001 to 100 equivalents with respect to compound (XXX), which is preferably 0.5 to 10 equivalents. Specific examples of acids include organic acids such as acetic acid, trifluoroacetic acid, and methanesulfonic acid; inorganic acids such as hydrochloric acid and sulfuric acid, and the like. An acid can be used at 0.001 to 100 equivalents with respect to compound (XXX), which is preferably 0.5 to 10 equivalents. Examples of other additives include dehydrating agents such as tetramethyl orthosilicate and methyl orthoformate; zinc chloride, titanium tetrachloride, lanthanum sulfate, magnesium sulfate-p-pyridinium p-toluenesulfonate, magnesium bromide, indium chloride, zirconium chloride, magnesium triflate, ytterbium(III)triflate (wherein (III) indicates that ytterbium is trivalent), scandium triflate, alumina, copper sulfate, titanium isopropoxide, titanium tetraethoxide, and other Lewis acids. An additive can be used at 0.001 to 100 equivalents with respect to compound (XXX), which is preferably 0.5 to 10 equivalents. Specific examples of inert solvents include water, acetonitrile; halogenated hydrocarbons such as chloroform and dichloromethane; aromatic hydrocarbons such as benzene and toluene; ether solvents such as DME, THF, and 1,4-dioxane; alcohol solvents such as methanol, ethanol, and 2-propanol; aprotic polar solvents such as DMF and NMP; mixture solvents thereof; and the like. The reaction temperature is selected from the range of about −20° C. to the boiling point of the solvent used.

Manufacturing Method 18

Compound (XXIX) can be manufactured, for example, by the manufacturing method described below by using compound (VI) as a raw material,

wherein Y, R¹, R², and R⁴ are defined the same as item 1, and m and n are defined the same as item 33. H of group —Y—H in formula (VI) is a hydrogen atom, PG¹, PG², and PG³ are each defined the same as the definition described in Manufacturing Method 1, T is defined the same as the definition described in Manufacturing Method 4, and PG⁶ is defined the same as the definition described in Manufacturing Method 15.

Step 18-1: Compound (XXIX) can be manufactured by a method in accordance with step 4-3 in Manufacturing Method 4 by using compound (VI) as a raw material.

Manufacturing Method 19

Compound (XXIX) can also be manufactured, for example, by the manufacturing method described below by using compound (XXXIII) as a raw material.

wherein Y, R¹, R², and R⁴ are defined the same as item 1, and m and n are defined the same as item 33. PG¹, PG², and PG³ are each defined the same as the definition described in Manufacturing Method 1, and PG⁶ is defined the same as the definition described in Manufacturing Method 15.

Step 19-1: Compound (XXIX) can be manufactured by a method in accordance with step 2-1 in Manufacturing Method 2 by using compound (XXXIII) as a raw material. Compound (XXXIII) can be manufactured, for example, in the same manner as Manufacturing Methods 20 to 22 described below or a known method from a corresponding raw material that can be purchased or prepared.

Manufacturing Method 20

Compound (XXXIII) can be manufactured, for example, by the manufacturing method described below by using compound (XV) as a raw material.

wherein Y, R¹, R², and R⁴ are defined the same as item 1, and m and n are defined the same as item 33. H of group —Y—H in formula (XV) is a hydrogen atom, PG¹, PG², and PG³ are each defined the same as the definition described in Manufacturing Method 1, T is defined the same as the definition described in Manufacturing Method 4, and PG⁶ is defined the same as the definition in Manufacturing Method 15.

Step 20-1: Compound (XXXIII) can be manufactured by a method in accordance with step 4-3 in Manufacturing Method 4 by using compound (XV) as a raw material.

Manufacturing Method 21

Compound (XXXIII) can also be manufactured, for example, by the manufacturing method described below by using compound (XVI) as a raw material.

wherein Y, R¹, R², and R⁴ are defined the same as item 1, and m and n are defined the same as item 33. H of group —Y—H in formula (XVI) is a hydrogen atom, PG¹, PG², and PG³ are each defined the same as the definition described in Manufacturing Method 1, T is defined the same as the definition described in Manufacturing Method 4, and PG⁶ is defined the same as the definition described in Manufacturing Method 15.

Step 21-1: Compound (XXXIV) can be manufactured by a method in accordance with step 4-3 in Manufacturing Method 4 by using compound (XVI) as a raw material.

Step 21-2: Compound (XXXIII) can be manufactured by a method in accordance with step 5-2 in Manufacturing Method 5 by using compound (XXXIV) as a raw material.

Manufacturing Method 22

Compound (XXXIII) can also be manufactured, for example, by the manufacturing method described below by using compound (XVIII) as a raw material.

wherein Y, R¹, R², and R⁴ are defined the same as item 1, and m and n are defined the same as item 33. H of group —Y—H in formula (XVIII) is a hydrogen atom, PG¹, PG², and PG³ are each defined the same as the definition described in Manufacturing Method 1, T is defined the same as the definition described in Manufacturing Method 4, and PG⁶ is defined the same as the definition described in Manufacturing Method 15.

Step 22-1: Compound (XXXV) can be manufactured by a method in accordance with step 4-3 in Manufacturing Method 4 by using compound (XVIII) as a raw material.

Step 22-2: Compound (XXXIII) can be manufactured by a method in accordance with step 6-5 in Manufacturing Method 6 by using compound (XXXV) as a raw material.

Manufacturing Method 23

A compound of formula (III) represented by formula (III-2) can be manufactured, for example, by the manufacturing method described below by using compound (XXXIII) as a raw material.

wherein Y, L³, L⁴, R¹, R², R⁴, and R³ are defined the same as item 1, and m and n are defined the same as item 33. PG¹, PG², and PG³ are each defined the same as the definition described in Manufacturing Method 1, T is defined the same as the definition described in Manufacturing Method 4, and PG⁶ is defined the same as the definition described in Manufacturing Method 15.

Step 23-1: Compound (XXXVI) can be manufactured by a method in accordance with step 15-1 in Manufacturing Method 15 by using compound (XXXIII) as a raw material.

Step 23-2: Compound (XIV-1) can be manufactured by a method in accordance with step 15-2 in Manufacturing Method 15, step 16-1 in Manufacturing Method 16, or step 17-1 in Manufacturing Method 17 by using compound (XXXVI) as a raw material.

Step 23-3: Compound (III-2) can be manufactured by a method in accordance with step 1-1, step 1-1-1, or step 1-1-2 in Manufacturing Method 1 (same as step 12-1 in Manufacturing Method 12) by using compound (XIV-1) as a raw material.

Manufacturing Method 24

A compound represented by formula (III-2) can be manufactured, for example, by the manufacturing method described below by using compound (XXVIII) as a raw material.

wherein Y, L³, L⁴, R¹, R², R⁴, and R⁵ are defined the same as item 1, and m and n are defined the same as item 33. H of group —Y—H in formula (XXVIII) is a hydrogen atom, T is defined the same as the definition described in Manufacturing Method 4, and PG⁶ is defined the same as the definition described in Manufacturing Method 15.

Step 24-1: Compound (XXXVII) can be manufactured by a method in accordance with step 4-3 in Manufacturing Method 4 by using compound (XXVIII) as a raw material.

Step 24-2: Compound (XXXVIII) can be manufactured by a method in accordance with step 13-6 in Manufacturing Method 13 by using compound (XXXVII) as a raw material.

Step 24-3: Compound (XXXIX) can be manufactured by a method in accordance with step 15-1 in Manufacturing Method 15 by using compound (XXXVIII) as a raw material.

Step 24-4: Compound (III-2) can be manufactured by a method in accordance with step 15-2 in Manufacturing Method 15, step 16-1 in Manufacturing Method 16, or step 17-1 in Manufacturing Method 17 by using compound (XXXIX) as a raw material.

Manufacturing Method 25

Compound (XXXVII) can also be manufactured, for example, by the manufacturing method described below by using compound (XX) as a raw material.

wherein Y, R¹, R², and R⁴ are defined the same as item 1, and m and n are defined the same as item 33. H of group —Y—H in formula (XX) is a hydrogen atom, PG¹ is defined the same as the definition described in Manufacturing Method 1, T is defined the same as the definition described in Manufacturing Method 4, PG³ is defined the same as the definition described in Manufacturing Method 6, and PG⁶ is defined the same as the definition described in Manufacturing Method 15.

Step 25-1: Compound (XXXX) can be manufactured by a method in accordance with step 4-3 in Manufacturing Method 4 by using compound (XX) as a raw material.

Step 25-2: Compound (XXXXI) can be manufactured by a method in accordance with step 6-2 in Manufacturing Method 6 by using compound (XXXX) as a raw material.

Step 25-3: Compound (XXXXII) can be manufactured by a method in accordance with step 4-2 in Manufacturing Method 4 by using compound (XXXXI) as a raw material.

Step 25-4: Compound (XXXVII) can be manufactured by a method in accordance with step 13-5 in Manufacturing Method 13 by using compound (XXXXII) as a raw material.

Manufacturing Method 26

A compound represented by formula (4a) defined in item 19 (hereinafter, also referred to as compound (4a)) and a compound represented by formula (4b) (hereinafter, also referred to as compound (4b)) can be manufactured, for example, by the manufacturing method described below by using compound (II-1) or compound (III-1) as a raw material,

wherein A, X, Y, L³, L⁴, R¹, R², R⁴, and R³ are defined the same as any of items 1 to 19. PG¹, PG², and PG³ in formula (II-1) are each defined the same as the definition described in Manufacturing Method 1.

Step 26-1: Compound (4a) can be manufactured by a method in accordance with step 1-1, step 1-1-1, or step 1-1-2 in Manufacturing Method 1 by using compound (II-1) as a raw material. Compound (4b) can also be obtained by a method in accordance with Manufacturing Method 3, by using compound (4a) as a raw material or in a step of manufacturing compound (4a).

Step 26-2: Compound (4a) can be manufactured by a method in accordance with step 2-1 in Manufacturing Method 2 by using compound (III-1) as a raw material. In the same manner, compound (4b) can be obtained in accordance with Manufacturing Method 3, by using compound (4a) as a raw material or in a step of manufacturing compound (4a).

Manufacturing Method 27

Compound (4a) and compound (4b) defined in item 19 represented by formula (4a-2) and formula (4b-2) described below can be manufactured, for example, by the manufacturing method described below by using compound (II-2) or compound (III-2) as a raw material.

wherein X, Y, L³, L⁴, R¹, R², R⁴, and R⁵ are defined the same as any of items 1 to 19, and m and n are defined the same as item 33. PG¹, PG 2, and PG³ in formula (II-2) are each defined the same as the definition described in Manufacturing Method 1.

Step 27-1: Compound (4a-2) can be manufactured by a method in accordance with step 1-1, step 1-1-1, or step 1-1-2 in Manufacturing Method 1 by using compound (II-2) as a raw material. Compound (4b-2) can also be obtained by a method in accordance with Manufacturing Method 3, by using compound (4a-2) as a raw material or in a step of manufacturing compound (4a-2).

Step 27-2: Compound (4a-2) can be manufactured by a method in accordance with step 2-1 in Manufacturing Method 2 by using compound (III-2) as a raw material. In the same manner, compound (4b-2) can be obtained by a method in accordance with Manufacturing Method 3, by using compound (4a-2) as a raw material or in a step of manufacturing compound (4a-2).

Manufacturing Method 28

Compound (4a) and compound (4b) defined in item 19 represented by formula (4a-3) and formula (4b-3) described below can be manufactured, for example, by the manufacturing method described below by using compound (II-3) as a raw material.

wherein X, Y, L⁴, R¹, R², R⁴, and R⁵ are defined the same as any of items 1 to 19, and m and n are defined the same as item 33. PG¹, PG², and PG³ in formula (II-3) are each defined the same as the definition described in Manufacturing Method 1.

Step 28-1: Compound (4a-3) can be manufactured by a method in accordance with step 1-1, step 1-1-1, or step 1-1-2 in Manufacturing Method 1 by using compound (II-3) as a raw material. Compound (4b-3) can be obtained by a method in accordance with Manufacturing Method 3, by using compound (4a-3) as a raw material or in a step of manufacturing compound (4a-3).

Manufacturing Method 29

Compound (4a) and compound (4b) defined in item 19 represented by formula (4a-4) and formula (4b-4) described below can be manufactured, for example, by the manufacturing method described below by using compound (II-4) as a raw material.

wherein X, Y, L⁴, R¹, R², R⁴, and R⁵ are defined the same as any of items 1 to 19, and m and n are defined the same as item 33. R⁶ is defined the same as the definition described in Manufacturing Method 17, and PG¹, PG², and PG³ in formula (II-4) are each defined the same as the definition described in Manufacturing Method 1.

Step 29-1: Compound (4a-4) can be manufactured by a method in accordance with step 1-1, step 1-1-1, or step 1-1-2 in Manufacturing Method 1 by using compound (II-4) as a raw material. Compound (4b-4) can be obtained by a method in accordance with Manufacturing Method 3, by using compound (4a-4) as a raw material or in a step of manufacturing compound (4a-4).

The intermediate and compound of interest in the manufacturing methods described above can be isolated and purified by subjecting them to a purification method that is commonly used in organic synthesis chemistry, e.g., neutralization, filtration, extraction, washing, drying, concentration, recrystallization, various chromatography, or the like. Each intermediate can also be subjected to the subsequent reaction without any particular purification.

Optically active forms of the compound of the invention can be manufactured by using an optically active starting material or intermediate, or by optically resolving a racemate of the final product or intermediate. Examples of optical resolution methods include physical separation methods using an optically active column and chemical separation methods such as fractional crystallization method. A diastereomer of the compound of the invention can be manufactured by, for example, a separation method such as column chromatography or fractional crystallization.

A pharmaceutically acceptable salt of a compound represented by formula (1a) or (1b) can be manufactured by, for example, mixing a compound represented by formula (1a) or formula (1b) with a pharmaceutically acceptable acid or base in a solvent such as water, methanol, ethanol, 2-propanol, ethyl acetate, or acetone, but the manufacturing method is not limited thereto.

As used herein, “or” is used when “at least one or more” of the listed matters in the sentence can be employed. When explicitly described herein as “within the range of two values”, the range also includes the two values themselves.

Reference literatures such as scientific literatures, patents, and patent applications cited herein are incorporated herein by reference to the same extent that the entirety of each document is specifically described. The US patent publications corresponding to the aforementioned prior art documents, i.e., Patent Literatures 1 to 10 (Patent Literature 1: US 2014/0194382A1; US 2014/0194385A1; Patent Literature 2: US 2014/0194381A1; US 2014/0194384A1; Patent Literature 3: US 2017/0088561A1; Patent Literature 4: US 2017/0136047A1; Patent Literature 5: US 2018/051041A1; Patent Literature 6: US 2014/0171390A1; Patent Literature 7: US 2014/0194386A1; Patent Literature 8: US 2016/0024121A1; Patent Literature 9: US 2015/0361107A1; US 2015/0361108A1; Patent Literature 10: US 2018/0002351A1) are also incorporated herein by reference to the same extent that the entirety of each document is specifically described.

As described above, the present invention has been described while showing preferred embodiments to facilitate understanding. The present invention is described hereinafter based on Examples. The above descriptions and the following Examples are not provided to limit the present invention, but for the sole purpose of exemplification. Thus, the scope of the present invention is not limited to the embodiments and Examples specifically described herein and is limited only by the scope of claims.

EXAMPLES

While the present invention is described more specifically with Reference Examples, Examples, and Test Examples hereinafter, the preset invention is not limited thereto.

Compounds were identified using proton nuclear magnetic resonance spectrum (¹H-NMR), liquid chromatography-mass spectrometry (LCMS), or the like. Tetramethylsilane was used as an internal standard for nuclear magnetic resonance spectrum.

For column chromatography in the Reference Examples and Examples, Yamazen Corporation's silica gel column, YMC's ODS-A column, YMC's YMC-Actus Triart C18, or YMC's YMC-Actus pro C18 were used. For TLC (silica gel plate) in purification using a thin layer chromatography (TLC), Silica gel 60F254 (Merck) was used, and for TLC (NH silica gel plate), TLC plate NH (Fuji Silysia) was used.

Various data described in the Reference Examples and Example were obtained with the following equipment.

NMR spectrum: 400 MHz or 270 MHz: JEOL JNM-AL series AL400 or JEOL EX270

LC-MS spectrum: Waters ACQUITY™ UltraPerformance LC

The compound names described in the Reference Examples and Examples were named using ACD/Name (ACD/Labs 12.0, Advanced Chemistry Development Inc.), which are not necessarily in accordance with the IUPAC nomenclature.

*1 and *2 appended to asymmetric carbon atoms in the structural formulas in the Reference Examples and the Examples indicate that the configuration of the carbon atom is not a racemate of a mixture of any ratio, but is substantially independent. If, for example, there are descriptions of structures of a compound (isomer 1) having a 3-membered ring (cyclopropane ring) or the three-membered ring further forming a condensed ring structure and having two *1 appended two asymmetric carbons constituting the three-membered ring (corresponding to two bridgehead position carbons in case of a condensed ring structure) and compound (isomer 2) similarly appended with two *2, this indicates that two bonds to three-membered ring methylene carbon from the two symmetric carbons in the same molecular structure have a configuration orientated toward the same direction in either a direction from the page surface to the backside or the front side (i.e., cis configuration), and indicates that isomer 1 and isomer 2 are different isomers. Specifically, this indicates that if one of isomer 1 and isomer 2 has a configuration in which the two bonds to a three-membered ring methylene carbon from two asymmetric carbons is oriented from the page surface to the back side, the other isomer is a configuration in which the bonds are oriented in the direction from the page surface to the front side, or the two isomers are enantiomers of each other with respect to the partial structure of the two asymmetric carbons. For example, the following table shows that the relationship between isomer 1 and isomer 2 is either case 1 or case 2 (the denotation describing a hydrogen atom (left side) and a denotation omitting a hydrogen atom (right side) for a stereochemical structure described in parallel in the following table are synonymous herein).

TABLE 2 isomer 1 Isomer 2 Examples of description of isomer

Case 1

Case 2

The measuring conditions (hereinafter, also referred to as the measurement methods) for a high performance liquid chromatography-mass spectrometry (LCMS) system are described below. The observed mass spectrometry value [MS (m/z)] is indicated by [M+1]⁺ (or denoted as [M+H]⁺), etc., and the time of retention at which the mass spectrometry value was observed is indicated by Rt (min). The measurement conditions A to I used for measurement are denoted in each actual measurement value. For example, “LCMS: [M+H]⁺/Rt=620/1.32^(A)” expresses that measurement was taken under measurement condition A.

Measurement Condition A

Measuring equipment: Waters ACQUITY™ UltraPerformance LC

Column: ACQUITY UPLC BEH C18 1.7 μm 2.1×30 mm column

Solvent: solution A: 0.05% HCOOH/H₂O, solution B: CH₃CN

Gradient Condition:

0.0 to 1.3 minutes; A/B=99/1 to 5/95 (linear gradient)

-   -   1.3 to 1.5 minutes; A/B=99/1

Flow rate: 0.80 mL/min

UV: 220 nm, 254 nm

Column temperature: 40° C.

Measurement Condition B

Measuring equipment: Waters ACQUITY™ UltraPerformance LC

Column: ACQUITY UPLC BEH C18 1.7 μm 2.1×30 mm column

Solvent: solution A: 0.05% HCOOH/H₂O, solution B: CH₃CN

Gradient Condition:

0.0 to 1.3 minutes; A/B=90/10 to 5/95 (linear gradient)

1.3 to 1.5 minutes; A/B=90/10

Flow rate: 0.80 mL/min

UV: 220 nm, 254 nm

Column temperature: 40° C.

Measurement Condition C

Measuring equipment: Waters ACQUITY™ UltraPerformance LC

Column: ACQUITY UPLC BEH C18 1.7 μm 2.1×30 mm column

Solvent: solution A: 0.05% HCOOH/H₂O, solution B: CH₃CN

Gradient Condition:

0.0 to 1.3 minutes; A/B=60/40 to 5/95 (linear gradient)

1.3 to 1.5 minutes; A/B=60/40

Flow rate: 0.80 mL/min

UV: 220 nm, 254 nm

Column temperature: 40° C.

Measurement Condition D

Measuring equipment: Shimadzu LCMS-2020

Column: Phenomenex Kinetex 1.7 μm C18 (50 mm×2.10 mm)

Solvent: solution A: 0.05% TFA/H₂O, solution B: CH₃CN

Gradient Condition:

0.0 to 1.9 minutes; A/B=90/10 to 1/99 (linear gradient)

1.91 to 3.00 minutes; A/B=1/99

Flow rate: 0.50 mL/min

UV: 220 nm, 254 nm

Column temperature: 40° C.

Measurement Condition E

Measuring equipment: Shimadzu LCMS-2020

Column: Phenomenex Kinetex 1.7 μm C18 (50 mm×2.10 mm)

Solvent: solution A: 0.05% TFA/H₂O, solution B: CH₃CN

Gradient Condition:

0.0 to 1.9 minutes; A/B=40/60 to 1/99 (linear gradient)

1.91 to 3.00 minutes; A/B=1/99

Flow rate: 0.50 mL/min

UV: 220 nm, 254 nm

Column temperature: 40° C.

Measurement Condition F

Measuring equipment: Shimadzu LCMS-2020

Column: Phenomenex Kinetex 1.7 μm C18 (50 mm×2.10 mm)

Solvent: solution A: 0.05% TFA/H₂O, solution B: CH₃CN

Gradient Condition:

0.0 to 1.9 minutes; A/B=99/1 to 1/99 (linear gradient)

1.91 to 3.00 minutes; A/B=1/99

Flow rate: 0.50 mL/min

UV: 220 nm, 254 nm

Column temperature: 40° C.

Measurement Condition G

Measuring equipment: Waters AQUITY™ UPLC H-Class System

Column: ACQUITY UPLC HSS T3 1.8 μm 2.1×35 mm column

Solvent: solution A: 0.1% HCOOH/H₂O, solution B: 0.1% HCOOH/CH₃CN

Gradient Condition:

0.0 to 2.4 minutes; A/B=90/10 to 0/100 (linear gradient)

2.4 to 3.2 minutes; A/B=0/100

Flow rate: 0.7 mL/min

UV: 190 to 800 nm

Column temperature: 40° C.

Measurement Condition H

Measuring equipment: Waters ACQUITY™ UltraPerformance LC

Column: ACQUITY UPLC BEH C18 1.7 μm 2.1×30 mm column

Solvent: solution A: 0.06% HCOOH/H₂O, solution B: 0.06% HCOOH/CH₃CN

Gradient Condition:

0.0 to 1.3 minutes; A/B=98/2 to 4/96 (linear gradient)

1.3 to 1.5 minutes; A/B=98/2

Flow rate: 0.80 mL/min

UV: 220 nm, 254 nm

Column temperature: 40° C.

Measurement Condition I

Measuring equipment: Shimadzu LCMS-2020

Column: Phenomenex Kinetex 1.7 μm C18 (50 mm×2.10 mm)

Solvent: solution A: 0.05% TFA/H₂O, solution B: CH₃CN

Gradient Condition:

0.0 to 1.9 minutes; A/B=70/30 to 1/99 (linear gradient)

1.91 to 3.00 minutes; A/B=1/99

Flow rate: 0.50 mL/min

UV: 220, 254 nm

Column temperature: 40° C.

Throughout the specification, the abbreviations described above and the following abbreviations are used, for example, in the Reference Examples, Examples, and Test Examples in some cases to simplify the description.

-   CDCl₃: deuterated chloroform -   CD₃OD: deuterated methanol -   s: singlet -   d: doublet -   t: triplet -   q: quadruplet -   m: multiplet -   br: broad -   dd: double doublet -   J: coupling constant -   Hz: Hertz -   δ: chemical shift -   min: minute -   THF: tetrahydrofuran -   DMF: N,N-dimethylformamide -   Me: methyl -   MeCN: acetonitrile -   Boc or BOC: tert-butoxycarbonyl -   tBu or ^(t)Bu or t-Bu: tert-butyl -   Cbz: benzyloxycarbonyl -   HCl: hydrogen chloride; represents hydrochloride especially when -   denoted in a structural formula of a basic compound such as amine -   LED: Light Emitting Diode -   MEPM: meropenem -   MIC: minimum inhibitory concentration -   HPLC: high performance liquid chromatography

Reference Example 1: tert-butyl 6-[(1-{[(tert-butoxycarbonyl)amino](1H-imidazol-4-yl)acetyl}azetidin-3-yl)oxy]-2-[(tert-butoxycarbonyl)oxy]-3-{2-[(3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}benzoate (derived from diastereomer 1-5-2; diastereo mixture)

Reference Example 1-1: tert-butyl 2,6-bis[(tert-butoxycarbonyl)oxy]-3-[(E)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethenyl]benzoate

Triethylamine (6.10 mL, 43.7 mmol), 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborolane (4.45 mL, 26.2 mmol), and bis(tri-tert-butylphosphine)palladium(0) (1.14 g, 2.22 mmol) were added to a toluene (87 mL) solution of tert-butyl 3-bromo-2,6-bis{(tert-butoxycarbonyl)oxy}benzoate (10.7 g, 21.9 mmol). The reaction mixture was stirred for 4 hours at 80° C. The reaction mixture was cooled to room temperature, and then filtered through celite to concentrate the filtrate. The resulting residue was purified by silica gel column chromatography to obtain the title compound (7.37 g).

¹H-NMR (400 MHZ, CDCl₃) δ: 7.61 (1H, d, J=8.5 Hz), 7.36 (1H, d, J=18.3 Hz), 7.08 (1H, d, J=8.5 Hz), 6.11 (1H, d, J=18.7 Hz), 1.54 (9H, s), 1.51 (9H, s), 1.51 (9H, s), 1.25 (12H, s).

Reference Example 1-2: benzyl 3-{2-(tert-butoxycarbonyl)-3-[(tert-butoxycarbonyl)oxy]-4-[(E)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethenyl]phenoxy}azetidine-1-carboxylate

Pyrrolidine (1.03 mL, 12.5 mmol) was added to a THF (33 mL) solution of the compound of Reference Example 1-1 (7.37 g, 13.1 mmol), and the reaction mixture was stirred for 1 hour at room temperature. 1-N-Cbz-3-hydroxyazetidine (3.26 g, 15.7 mmol) was added to the reaction mixture, which is referred to as mixture A hereinafter.

Tri-n-butylphosphine (8.18 mL, 32.8 mmol) was added to a toluene (65.5 mL) solution of N,N,N′,N′-tetramethylazodicarboxamide (6.71 g, 39.0 mmol) while cooling with ice. The reaction mixture was directly stirred for 10 minutes while cooling with ice. This is referred to as mixture B hereinafter.

Mixture A was added to mixture B while cooling with ice, and the newly produced reaction mixture was stirred for 2.5 hours at 65° C. The reaction mixture was cooled to room temperature, then the precipitate was filtered out, and the filtrate was concentrated. The resulting residue was purified by silica gel column chromatography to obtain the title compound (6.34 g).

¹H-NMR (400 MHZ, CDCl₃) δ: 7.51 (1H, d, J=8.7 Hz), 7.34-7.26 (7H, m), 6.41 (1H, d, J=8.7 Hz), 6.02 (1H, d, J=18.3 Hz), 5.09 (2H, s), 4.93-4.91 (1H, m), 4.35 (2H, dd, J=10.5, 6.4 Hz), 4.10-4.05 (2H, m), 1.54 (9H, s), 1.51 (9H, s), 1.25 (13H, s).

Reference Example 1-3: benzyl 3-{2-(tert-butoxycarbonyl)-3-[(tert-butoxycarbonyl)oxy]-4-[(Z)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethenyl]phenoxy}azetidine-1-carboxylate

Tris(2-phenylpyridinato)iridium(III) (5.5 mg, 0.0084 mmol) was added to an acetonitrile (0.5 mL) solution of the compound of Reference Example 1-2 (66 mg, 0.101 mmol), and the reaction mixture was stirred for 3.5 hours at room temperature under irradiation of a blue LED light (450 nm) under a nitrogen atmosphere. The reaction mixture was concentrated. The resulting residue was purified by silica gel column chromatography to obtain the title compound (35 mg).

¹H-NMR (400 MHZ, CDCl₃) δ: 7.55 (1H, d, J=8.5 Hz), 7.34-7.29 (5H, m), 7.05 (1H, d, J=14.6 Hz), 6.36 (1H, d, J=8.5 Hz), 5.63 (1H, d, J=14.6 Hz), 5.09 (2H, s), 4.93 (1H, t, J=6.4 Hz), 4.35 (2H, dd, J=10.1, 7.0 Hz), 4.09 (2H, dd, J=10.4, 4.3 Hz), 1.54 (9H, s), 1.48 (9H, s), 1.22 (12H, s).

Reference Example 1-4: benzyl 3-[2-(tert-butoxycarbonyl)-3-[(tert-butoxycarbonyl)oxy]-4-{(Z)-2-[(3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]ethenyl}phenoxy]azetidine-1-carboxylate

(1S,2S,3R,5R)-(+)-pinanediol (2.63 g, 15.5 mmol) was added to a THF (16.1 mL) solution of the compound of Reference Example 1-3 (2.52 g, 3.87 mmol), and the reaction mixture was stirred for 48 hours at room temperature. The reaction mixture was concentrated. The resulting residue was purified by silica gel column chromatography to obtain the title compound (1.76 g).

¹H-NMR (400 MHZ, CDCl₃) δ: 7.56 (1H, d, J=8.7 Hz), 7.35-7.30 (5H, m), 7.08 (1H, d, J=14.6 Hz), 6.36 (1H, d, J=8.7 Hz), 5.67 (1H, d, J=14.6 Hz), 5.09 (2H, s), 4.95-4.91 (1H, m), 4.35 (2H, dd, J=10.1, 6.4 Hz), 4.24 (1H, dd, J=8.9, 2.1 Hz), 4.10-4.06 (2H, m), 2.29-2.24 (1H, m), 2.19-2.14 (1H, m), 2.00 (1H, t, J=5.5 Hz), 1.89-1.85 (1H, m), 1.82-1.78 (1H, m), 1.54 (9H, s), 1.48 (9H, s), 1.35 (3H, s), 1.26 (3H, s), 1.19 (1H, d, J=11.0 Hz), 0.81 (3H, s).

Reference Example 1-5: benzyl 3-[2-(tert-butoxycarbonyl)-3-hydroxy-4-{2-[(3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}phenoxy]azetidine-1-carboxylate (diastereo mixture of diastereomer 1-5-1 and diastereomer 1-5-2)

A hexane (20.5 mL) solution of diethylzinc (20.5 mmol) (concentration: 1 mol/L) was dissolved in dichloromethane (14.7 mL), and diiodomethane (2.5 mL, 31.0 mmol) was slowly added at −78° C. The reaction mixture was stirred for 5 minutes while cooling with ice, then cooled again to −78° C. A dichloromethane (6 mL) solution of the compound of Reference Example 1-4 (1.76 g, 2.49 mmol) was added dropwise. The reaction mixture was stirred for 10 minutes at −78° C., then warmed to room temperature, and stirred for 2.5 hours at room temperature. An aqueous saturated ammonium chloride solution was added to the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed with saturated saline, then dried with anhydrous sodium sulfate, and filtered, and the filtrate was concentrated. The resulting residue was purified by silica gel column chromatography to obtain the title compound (847 mg) as a diastereo mixture of diastereomer 1-5-1 and diastereomer 1-5-2. The ratio of mixture of both isomers (1-5-1:1-5-2) was about 3:1 (according to ¹H-NMR integration ratio).

Reference Example 1-5-1: benzyl 3-[2-(tert-butoxycarbonyl)-3-hydroxy-4-{2-[(3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}phenoxy]azetidine-1-carboxylate (diastereomer 1-5-1)

¹H-NMR (400 MHZ, CDCl₃) δ: 11.71 (1H, s), 7.33-7.29 (5H, m), 7.12 (1H, d, J=8.6 Hz), 5.89 (1H, d, J=8.6 Hz), 5.10 (2H, s), 4.88-4.85 (1H, m), 4.36-4.30 (2H, m), 4.10-4.07 (2H, m), 4.01-3.97 (2H, m), 2.30-2.23 (1H, m), 2.06-1.98 (1H, m), 1.87 (1H, t, J=5.8 Hz), 1.75-1.73 (1H, m), 1.66-1.61 (1H, m), 1.46 (9H, s), 1.19 (3H, s), 1.10 (3H, s), 1.09-1.05 (2H, m), 0.79 (1H, d, J=11.0 Hz), 0.70 (3H, s), 0.52-0.45 (1H, m).

Reference Example 1-5-2: benzyl 3-[2-(tert-butoxycarbonyl)-3-hydroxy-4-{2-[(3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}phenoxy]azetidine-1-carboxylate (diastereomer 1-5-2)

¹H-NMR (400 MHZ, CDCl₃) δ: 11.67 (1H, s), 7.33-7.29 (5H, m), 7.09 (1H, d, J=8.6 Hz), 5.85 (1H, d, J=8.6 Hz), 5.11 (2H, s), 4.88-4.85 (1H, m), 4.36-4.30 (2H, m), 4.08-4.04 (2H, m), 4.01-3.97 (1H, m), 3.95-3.90 (1H, m), 2.30-2.23 (1H, m), 2.20-2.13 (1H, m), 1.87 (1H, t, J=5.8 Hz), 1.75-1.73 (1H, m), 1.66-1.61 (1H, m), 1.46 (9H, s), 1.19 (3H, s), 1.10 (3H, s), 1.09-1.05 (2H, m), 0.79 (1H, d, J=11.0 Hz), 0.71 (3H, s), 0.51-0.44 (1H, m).

Reference Example 1-6-1: benzyl 3-[2-(tert-butoxycarbonyl)-3-[(tert-butoxycarbonyl)oxy]-4-{2-[(3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}phenoxy]azetidine-1-carboxylate (diastereomer 1-6-1), and Reference Example 1-6-2: benzyl 3-[2-(tert-butoxycarbonyl)-3-[(tert-butoxycarbonyl)oxy]-4-{2-[(3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}phenoxy]azetidine-1-carboxylate (diastereomer 1-6-2)

Di-tert-butyl dicarbonate (0.637 mL, 2.74 mmol), triethylamine (0.382 mL, 2.74 mmol), and 4-dimethylaminopyridine (20.2 mg, 0.165 mmol) were added to a dichloromethane (5 mL) solution of the compound of Reference Example 1-5 (diastereo mixture) (847 mg, 1.37 mmol). The reaction mixture was stirred for 48 hours at room temperature. The reaction mixture was concentrated, the residue was dissolved in dichloromethane (5 mL), and di-tert-butyl dicarbonate (2.25 g, 10.3 mmol) and 4-dimethylaminopyridine (0.3 g, 2.46 mmol) were added. The reaction mixture was stirred for 4 hours at room temperature and 3 hours at 40° C. The reaction mixture was concentrated. The resulting residue was purified by silica gel column chromatography to separate and obtain the compound of Reference Example 1-6-1 (identified by TLC (silica gel plate) Rf value: 0.46 (hexane/ethyl acetate=2/1)) (285 mg) and the compound of Reference Example 1-6-2 (identified by TLC Rf value: 0.52 under the same condition as above) (95.3 mg) as different diastereomer 1-6-1 and diastereomer 1-6-2, respectively.

Reference Example 1-6-1: benzyl 3-[2-(tert-butoxycarbonyl)-3-[(tert-butoxycarbonyl)oxy]-4-{2-[(3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}phenoxy]azetidine-1-carboxylate (diastereomer 1-6-1)

LCMS: [M-Boc]⁺/Rt=617.6/1.433 min^(B)

¹H-NMR (400 MHZ, CDCl₃) δ: 7.34-7.28 (5H, m), 7.17 (1H, d, J=8.5 Hz), 6.33 (1H, d, J=8.5 Hz), 5.08 (2H, s), 4.90-4.85 (1H, m), 4.33-4.28 (2H, m), 4.07-3.99 (3H, m), 2.15-2.04 (3H, m), 1.85 (1H, t, J=5.5 Hz), 1.76-1.72 (1H, m), 1.52 (9H, s), 1.51 (9H, s), 1.34-1.29 (1H, m), 1.19 (3H, s), 1.13-1.01 (2H, m), 1.06 (3H, s), 0.99 (1H, d, J=11.0 Hz), 0.70 (3H, s), 0.39 (1H, td, J=9.6, 6.9 Hz).

Reference Example 1-6-2: benzyl 3-[2-(tert-butoxycarbonyl)-3-[(tert-butoxycarbonyl)oxy]-4-{2-[(3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}phenoxy]azetidine-1-carboxylate (diastereomer 1-6-2)

¹H-NMR (400 MHZ, CDCl₃) δ: 7.33-7.28 (5H, m), 7.14 (1H, d, J=8.5 Hz), 6.31 (1H, d, J=8.5 Hz), 5.09 (2H, s), 4.91-4.86 (1H, m), 4.35-4.28 (2H, m), 4.13-3.99 (2H, m), 3.93 (1H, dd, J=8.9, 2.1 Hz), 2.14-2.07 (1H, m), 1.95-1.90 (1H, m), 1.81 (2H, t, J=5.5 Hz), 1.76-1.73 (1H, m), 1.65 (1H, d, J=16.5 Hz), 1.53 (9H, s), 1.52 (9H, s), 1.18 (3H, s), 1.12-0.97 (2H, m), 1.07 (3H, s), 0.80 (1H, d, J=11.0 Hz), 0.71 (3H, s), 0.42-0.33 (1H, m).

Reference Example 1-7: tert-butyl 6-[(azetidin-3-yl)oxy]-2-[(tert-butoxycarbonyl)oxy]-3-{2-[(3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}benzoate hydrochloride (diastereomer derived from diastereomer 1-5-2)

Palladium/carbon (Pd: 10%, wetted with ca. 55% water, 37.8 mg) and an aqueous 1 mol/L hydrochloric acid solution (0.133 mL, 0.133 mmol) were added to a methanol (3 mL) solution of the compound of Reference Example 1-6-2 (95.3 mg, 0.133 mmol), and the reaction mixture was stirred at room temperature for 1.5 hours under a hydrogen atmosphere. The reaction mixture was filtered through celite, and the filtrate was concentrated. The resulting residue was purified by silica gel column chromatography to obtain the title compound (82 mg).

LCMS: [M+H]⁺/Rt=584.5/1.099 min^(B)

Reference Example 1: tert-butyl 6-[(1-{[(tert-butoxycarbonyl)amino](1H-imidazol-4-yl)acetyl}azetidin-3-yl)oxy]-2-[(tert-butoxycarbonyl)oxy]-3-{2-[(3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}benzoate (derived from diastereomer 1-5-2; diastereo mixture)

1-hydroxybenzotriazole (44.7 mg, 0.331 mmol), triethylamine (0.0461 mL, 0.331 mmol), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (63.4 mg, 0.331 mmol) were added to a DMF (2 mL) solution of [(tert-butoxycarbonyl)amino]-2-(1H-imidazol-4-yl)acetate (racemate) (50.6 mg, 0.210 mmol) while cooling with ice. The reaction mixture was stirred for 25 minutes while cooling with ice, then the compound of Reference Example 1-7 (82 mg, 0.132 mmol), triethylamine (0.02 mL), and 4-dimethylaminopyridine (4.8 mg, 0.039 mmol) were added. The reaction mixture was stirred for 16 hours at room temperature, then an aqueous saturated sodium hydrogen carbonate solution was added. The reaction mixture was extracted with ethyl acetate. The organic layer was washed with saturated saline, then dried with anhydrous sodium sulfate, and filtered, and the filtrate was concentrated. The resulting residue was purified by silica gel column chromatography to obtain the title compound (73.7 mg) as a diastereo mixture comprising two types of diastereomers due to the reagent used, i.e., [(tert-butoxycarbonyl)amino]-2-(1H-imidazol-4-yl) acetate, being a racemate and having an asymmetric center derived from diastereomer 1-5-2.

LCMS: [M+H]⁺/Rt=807.6/1.228 min^(A)

Reference Example 2: tert-butyl 6-[(1-{[(tert-butoxycarbonyl)amino](1H-imidazol-4-yl)acetyl}azetidin-3-yl)oxy]-2-[(tert-butoxycarbonyl)oxy]-3-{2-[(3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}benzoate (derived from diastereomer 1-5-1; diastereo mixture)

Reference Example 2-1: tert-butyl 6-[(azetidin-3-yl)oxy]-2-[(tert-butoxycarbonyl)oxy]-3-{2-[(3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}benzoate hydrochloride (diastereomer derived from diastereomer 1-5-1)

The compound of Reference Example 1-6-1 (101 mg) was used as a raw material, and a reaction and post-processing were performed in accordance with the same method as the method described in Reference Example 1-7 to obtain the title compound (81.8 mg).

LCMS: [M+H]⁺/Rt=584.6/1.095 min^(B)

Reference Example 2: tert-butyl 6-[(1-{[(tert-butoxycarbonyl)amino](1H-imidazol-4-yl)acetyl}azetidin-3-yl)oxy]-2-[(tert-butoxycarbonyl)oxy]-3-{2-[(3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}benzoate (derived from diastereomer 1-5-1; diastereo mixture)

The compound of Reference Example 2-1 (81.8 mg) was used as a raw material, and a reaction and post-processing were performed in accordance with the same method as the method described in Reference Example 1 to obtain the title compound (91.1 mg) as a diastereo mixture comprising two types of diastereomers due to the reagent used, i.e., [(tert-butoxycarbonyl)amino]-2-(1H-imidazol-4-yl) acetate, being a racemate and having an asymmetric center derived from diastereomer 1-5-1.

LCMS: [M+H]⁺/Rt=807.7/1.261 min^(A)

Reference Example 3: (2R)-2-[(tert-butoxycarbonyl)amino]-3-{3-[2-(tert-butoxycarbonyl)-3-[(tert-butoxycarbonyl)oxy]-4-{2-[(3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}phenoxy]azetidin-1-yl}-2-methylpropanoate (diastereomer derived from diastereomer 1-5-1)

Reference Example 3-1: tert-butyl 6-[(1-{(2R)-2-[(tert-butoxycarbonyl)amino]-3-methoxy-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-2-[(tert-butoxycarbonyl)oxy]-3-{2-[(3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}benzoate (diastereomer derived from diastereomer 1-5-1)

Palladium/carbon (Pd content: 10%, wetted with ca. 55% water, 36.7 mg) was added to a methanol (3 mL) solution of the compound of Reference Example 1-6-1 (108.5 mg, 0.151 mmol), and the reaction mixture was stirred for 1 hour under a hydrogen atmosphere at room temperature. The reaction mixture was filtered through celite, and the filtrate was concentrated. The resulting residue was dissolved in dichloromethane (2.5 mL), and methyl (2R)-2-[(tert-butoxycarbonyl)amino]-2-methyl-3-oxopropanoate (110 mg, 0.476 mmol), copper sulfate (13.1 mg, 0.082 mmol), and acetic acid (0.020 mL, 0.345 mmol) were added. The reaction mixture was stirred for 1 hour at room temperature. The reaction mixture was added with sodium triacetoxyborohydride (112 mg, 0.529 mmol) and stirred for 1 hour at room temperature. An aqueous saturated sodium hydrogen carbonate solution was added to the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed with saturated saline, then dried with anhydrous sodium sulfate, and filtered, and the filtrate was concentrated. The resulting residue was purified by silica gel column chromatography to obtain the title compound (102.7 mg).

LCMS: [M+H]⁺/Rt=799.45/1.154 min^(B)

Reference Example 3: (2R)-2-[(tert-butoxycarbonyl)amino]-3-{3-[2-(tert-butoxycarbonyl)-3-[(tert-butoxycarbonyl)oxy]-4-{2-[(3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}phenoxy]azetidin-1-yl}-2-methylpropanoate (diastereomer derived from diastereomer 1-5-1)

An aqueous 1 mol/L lithium hydroxide solution (0.77 mL, 0.77 mmol) was added to a THF (0.74 mL)-water (0.33 mL) mixture of the compound of Reference Example 3-1 (102.7 mg, 0.129 mmol) while cooling with ice, and the reaction mixture was stirred for 40 hours at room temperature. An aqueous 2 mol/L hydrochloric acid solution was added to the reaction mixture to achieve a pH near 4.0, and the reaction mixture was extracted with ethyl acetate. The organic layer was washed with saturated saline, dried with anhydrous sodium sulfate, and filtered, and the filtrate was concentrated to obtain the title compound (21.1 mg).

¹H-NMR (400 MHZ, CDCl₃) δ: 7.16 (1H, d, J=8.5 Hz), 6.41 (1H, d, J=8.5 Hz), 6.34 (1H, br s), 4.96-4.91 (1H, m), 4.86-4.79 (1H, m), 4.72-4.65 (1H, m), 4.02-3.90 (2H, m), 3.82 (1H, d, J=12.2 Hz), 3.73-3.67 (1H, m), 3.57 (1H, d, J=12.2 Hz), 2.12-2.03 (4H, m), 1.84 (1H, t, J=5.5 Hz), 1.75-1.72 (1H, m), 1.53 (9H, s), 1.51 (9H, s), 1.40 (9H, s), 1.33-1.27 (1H, m), 1.20 (3H, d, J=2.4 Hz), 1.11-1.02 (4H, m), 1.05 (3H, s), 1.00 (1H, d, J=11.0 Hz), 0.71 (3H, s), 0.37 (1H, td, J=9.6, 6.9 Hz).

Reference Example 4: tert-butyl 6-[(1-{[(tert-butoxycarbonyl)amino](1H-imidazol-4-yl)propanoyl}azetidin-3-yl)oxy]-2-[(tert-butoxycarbonyl)oxy]-3-{2-[(3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}benzoate (derived from diastereomer 1-5-2; diastereo mixture)

The compound of Reference Example 1-7 (25.7 mg) was used as a raw material, and [(tert-butoxycarbonyl)amino]-2-(1H-imidazol-4-yl)propionate (racemate) was used instead of [(tert-butoxycarbonyl)amino]-2-(1H-imidazol-4-yl)acetate (racemate), and a reaction and post-processing were performed in accordance with the same method as the method described in Reference Example 1 to obtain the title compound (13.8 mg) as a diastereo mixture comprising two types of diastereomers due to the reagent used, i.e., [(tert-butoxycarbonyl)amino]-2-(1H-imidazol-4-yl) propionate, being a racemate and having an asymmetric center derived from diastereomer 1-5-2.

LCMS: [M+H]⁺/Rt=821.63/1.295 min^(A)

Reference Example 5: tert-butyl 6-[(1-{[(tert-butoxycarbonyl)amino](1H-imidazol-4-yl)propanoyl}azetidin-3-yl)oxy]-2-[(tert-butoxycarbonyl)oxy]-3-{2-[(3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}benzoate (derived from diastereomer 1-5-1; diastereo mixture)

The compound of Reference Example 2-1 (27 mg) was used as a raw material, and [(tert-butoxycarbonyl)amino]-2-(1H-imidazol-4-yl)propionate (racemate) was used instead of [(tert-butoxycarbonyl)amino]-2-(1H-imidazol-4-yl) acetate (racemate), and a reaction and post-processing were performed in accordance with the same method as the method described in Reference Example 1 to obtain the title compound (11.8 mg) as a diastereo mixture comprising two types of diastereomers due to the reagent used, i.e., [(tert-butoxycarbonyl)amino]-2-(1H-imidazol-4-yl) propionate, being a racemate and having an asymmetric center derived from diastereomer 1-5-1.

LCMS: [M+H]⁺/Rt=821.54/1.244 min^(A)

For example, the compounds of Reference Examples 1, 2, 4, and 5 that are diastereo mixtures can be optically resolved by chiral chromatography under the following condition. Accordingly, intermediates of Reference Examples can be further fractionated and identified to create and identify any of each diastereomer for the diastereo mixture of the compounds of the Examples described below.

Column: CHIRALPAK IG 20 mmφ×250 mm (Daicel Corporation)

Mobile phase: diethylamine/ethyl acetate (diethylamine: 0.1%)

Reference Example (R)-6: tert-butyl 6-({1-[(2R)-2-[(tert-butoxycarbonyl)amino]-2-(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy)-2-[(tert-butoxycarbonyl)oxy]-3-{(2-[(3aS,4S,6S)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}benzoate Reference Example (S)-6: tert-butyl 6-({1-[(2S)-2-[(tert-butoxycarbonyl)amino]-2-(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy)-2-[(tert-butoxycarbonyl)oxy]-3-{(2-[(3aS,4S,6S)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}benzoate

The compound of Reference Example 1 (amount loaded per injection: 6.17 mg) was dissolved in 0.300 mL of ethyl acetate. Isomers were obtained by optical resolution through chiral chromatography under the following conditions.

Column: CHIRALPAK IC 20 mmφ×250 mm (Daicel Corporation)

Mobile phase: hexane/ethanol (1:1)

Flow rate: 10 mL/min

Temperature: 40° C.

Column retention times for both optical isomers were as follows.

Reference Example (R)-6: 9.25 min

Reference Example (S)-6: 13.04 min

Reference Example 7: tert-butyl 2-[(tert-butoxycarbonyl)oxy]-6-({1-[(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy)-3-{2-[(3aS,4S,6S)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}benzoate

N,N-diisopropylethylamine (0.199 mL, 0.684 mmol) was added to a THF solution (0.9 mL) of the compound of Reference Example 1-7 (106 mg, 0.171 mmol), and 2-(1H-imidazol-4-yl)acetic acid hydrochloride (36 mg, 0.222 mmol) and pyBOP (133 mg, 0.256 mmol) were added in an ice bath. After confirming completion of the reaction by TLC, an aqueous saturated sodium hydrogen carbonate solution was added. The reaction mixture was extracted with ethyl acetate. The organic layer was washed with saturated saline, then dried with anhydrous sodium sulfate, and filtered, and the filtrate was concentrated. The resulting residue was purified by silica gel column chromatography (chloroform/methanol) to obtain the title compound (110 mg).

LCMS: [M+H]⁺/Rt=692.40/0.686 min^(C)

Reference Example 8: tert-butyl 2-[(tert-butoxycarbonyl)oxy]-6-({1-[N-(tert-butoxycarbonyl)-D-seryl]azetidin-3-yl}oxy)-3-{2-[(3aS,4S,6S)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}benzoate

Palladium/carbon (Pd: 10%, wetted with ca. 55% water, 10 mg) was added to a methanol (2 mL) solution of the compound of Reference Example 1-6-1 (100 mg, 0.139 mmol), and the reaction mixture was stirred for 30 minutes under a hydrogen atmosphere at room temperature. The reaction mixture was filtered through celite, and the filtrate was concentrated. The resulting residue was dissolved in DMF (1 mL) as solution A.

DMT-MM (46.3 mg, 0.167 mmol) was added to a methanol solution (1 mL) of N-tert-butoxycarbonyl-D-serine (43 mg, 0.209 mmol), and the reaction mixture was stirred for 15 minutes at room temperature. Solution A was added, and the reaction mixture was stirred for 1 hour at room temperature. Saturated saline was added to the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed with saturated saline, then dried with anhydrous sodium sulfate, and filtered, and the filtrate was concentrated. The resulting residue was purified by silica gel column chromatography (dichloromethane/methanol) to obtain the title compound (112 mg) as a colorless amorphous compound.

¹H-NMR (270 MHz, CDCl₃) δ: 7.24-7.19 (1H, m), 6.39-6.35 (1H, m), 5.56-5.45 (1H, m), 4.97-4.91 (1H, m), 4.75-4.56 (1H, m), 4.44-4.22 (3H, m), 4.09-4.03 (2H, m), 3.88-3.82 (1H, m), 3.74-3.67 (1H, m), 2.19-2.03 (3H, m), 1.91-1.85 (1H, m), 1.80-1.74 (1H, m), 1.63-1.48 (19H, m), 1.45-1.22 (11H, m), 1.17-0.84 (7H, m), 0.73 (3H, s), 0.46-0.36 (1H, m).

Reference Example 9: tert-butyl (2S,4R)-2-{3-[2-(tert-butoxycarbonyl)-3-[(tert-butoxycarbonyl)oxy]-4-{2-[(3aS,4S,6S)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}phenoxy]azetidine-1-carbonyl}-4-hydroxypyrrolidine-1-carboxylic acid

The compound of Reference Example 1-6-1 (100 mg, 0.139 mmol) and trans-N-(tert-butoxycarbonyl)-4-hydroxy-L-proline (48.3 mg, 0.209 mmol) were used as a raw material, and a reaction and post-processing were performed in accordance with the same method as the method described in Reference Example 8 to obtain the title compound (110 mg) as a colorless amorphous compound.

¹H-NMR (270 MHz, CDCl₃) δ: 9.27-8.66 (1H, m), 7.26-7.23 (1H, m), 6.38-6.35 (1H, m), 5.48-5.27 (1H, m), 5.04-4.87 (1H, m), 4.58-4.29 (4H, m), 4.23-3.95 (3H, m), 3.70-3.42 (2H, m), 2.18-2.04 (6H, m), 1.90-1.41 (23H, m), 1.37-1.22 (7H, m), 1.16-1.00 (6H, m), 0.73 (3H, s), 0.46-0.36 (1H, m).

Each of Reference Example compounds 10 to 13 shown in Table 4 was obtained by performing a reaction, post-processing, and purification in accordance with the same method as the method described in Reference Example 1 while using the compound of Reference Example 1-7 and carboxylic acid corresponding to each of the following Reference Examples as a raw material.

TABLE 4 Reference Example Structural formula LCMS and/or NMR 10

LCMS: [M + H]⁺/Rt = 887.46/1.386 min^(C) 11

LCMS: [M + H]⁺/Rt = 785.37/1.410 min^(A) ¹H-NMR (CDCl₃) δ: 7.16 (1H, d, J = 8.5 Hz), 6.32 (1H, d, J = 8.5 Hz), 5.09-4.96 (1H, m), 4.91-4.86 (1H, m), 4.67-4.60 (1H, m), 4.42- 4.28 (2H, m), 4.12-3.97 (2H, m), 3.92 (1H, dd, J = 8.5, 1.8 Hz), 3.53-3.44 (1H, m), 2.16-2.07 (2H, m), 1.99-1.91 (1H, m), 1.85-1.80 (1H, m), 1.78-1.74 (1H, m), 1.66-1.62 (1H, m), 1.53 (9H, s), 1.51 (9H, s), 1.44-1.39 (12H, m), 1.25 (3H, s), 1.19 (3H, s), 1.11-1.06 (1H, m), 1.02-0.97 (1H, m), 0.87-0.80 (1H, m), 0.72 (3H, s), 0.38-0.34 (1H, m). 12

LCMS: [M + H]⁺/RT = 811.39/1.479 min^(A) ¹H-NMR (CDCl₃) δ: 7.15 (1H, d, J = 8.5 Hz), 6.33 (1H, d, J = 8.5 Hz), 4.93-4.88 (1H, m), 4.54-4.22 (3H, m), 4.14-4.02 (2H, m), 3.96- 3.90 (2H, m), 3.85-3.79 (2H, m), 3.56-3.48 (1H, m), 3.39-3.30 (1H, m), 2.90-2.82 (1H, m), 2.66-2.59 (1H, m), 2.33-2.26 (1H, m), 2.18-2.08 (2H, m), 1.96-1.91 (1H, m), 1.84- 1.80 (1H, m), 1.78-1.74 (1H, m), 1.68-1.61 (1H, m), 1.54 (9H, s), 1.52 (9H, s), 1.44 (9H, s), 1.27-1.24 (3H, m), 1.19 (3H, s), 1.11-1.05 (1H, m), 1.03-0.98 (1H, m), 0.85-0.79 (1H, m), 0.72 (3H, s), 0.39-0.34 (1H, m). 13

LCMS: [M + H]⁺/RT = 811.20/2.60 min^(A)

Reference Example 14: (2R)-2-[(tert-butoxycarbonyl) amino]-3-{3-[2-(tert-butoxycarbonyl)-3-[(tert-butoxycarbonyl)oxy]-4-{2-[(3aS,4S,6S)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}phenoxy]azetidin-1-yl}-2-methylpropanoate

The compound of Reference Example 1-6-2 (0.183 g, 0.255 mmol) was used as a raw material, and a reaction and post-processing were performed in accordance with the same method as the method described in Reference Example 3 to obtain the title compound (109 mg).

LCMS: [M+H]⁺/RT=785/2.067 min^(D)

Reference Example 15: tert-butyl 6-[(1-{(2R)-2-[(tert-butoxycarbonyl)amino]-3-[(2-hydroxyethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-2-[(tert-butoxycarbonyl)oxy]-3-{2-[(3aS,4S,6S)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}benzoate

1-hydroxybenzotriazole (50.1 mg, 0.371 mmol), triethylamine (0.0517 mL, 0.371 mmol), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (71.1 mg, 0.371 mmol) were added to a DMF solution (1.2 mL) of the compound of Reference Example 14 (116 mg, 0.148 mmol) in an ice bath. The reaction mixture was stirred for 30 minutes at room temperature, and then 2-aminoethanol (0.020 mL, 0.331) was added in an ice bath. The reaction mixture was stirred for 6 hours at room temperature, and then an aqueous saturated sodium hydrogen carbonate solution was added. The reaction mixture was extracted with ethyl acetate. The organic layer was washed with saturated saline, then dried with anhydrous sodium sulfate, and filtered, and the filtrate was concentrated. The resulting residue was purified by silica gel column chromatography to obtain the title compound as a diastereo mixture (37.6 mg).

LCMS: [M+H]⁺/RT=828.51/1.195 min^(A)

Reference Example 16: tert-butyl 6-[(1-{(2R)-3-[(2-amino-2-oxoethyl)amino]-2-[(tert-butoxycarbonyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-2-[(tert-butoxycarbonyl)oxy]-3-{2-[(3aS,4S,6S)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}benzoate

Glycinamide hydrochloride (69 mg, 0.624 mmol), N,N-diisopropylethylamine (0.322 mL, 1.85 mmol), and TBTU (201.7 mg, 0.628 mmol) were added to a dichloromethane solution (8.2 mL) of the compound of Reference Example 14 (322.4 mg, 0.411 mmol) in an ice bath. The reaction mixture was stirred for 30 minutes in an ice bath, and then the reaction mixture was stirred for 4 hours at room temperature. An aqueous saturated sodium hydrogen carbonate solution was added to the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed with saturated saline, then dried with anhydrous sodium sulfate, and filtered, and the filtrate was concentrated. The resulting residue was purified by silica gel column chromatography to obtain the title compound (323.4 mg) as a white solid.

LCMS: [M+H]⁺/RT=841.67/1.117 min^(A)

¹H-NMR (CD₃OD) δ: 7.20 (1H, d, J=8.5 Hz), 6.58 (1H, d, J=8.5 Hz), 4.00 (1H, dd, J=8.5, 1.8 Hz), 3.89-3.85 (2H, m), 3.82-3.76 (2H, m), 3.26-3.22 (1H, m), 3.20-3.17 (1H, m), 2.95 (2H, dd, J=18.0, 13.1 Hz), 2.21-2.15 (1H, m), 2.08 (1H, dd, J=15.6, 7.6 Hz), 1.97-1.91 (1H, m), 1.89 (1H, s), 1.76 (2H, d, J=6.1 Hz), 1.67 (1H, d, J=12.8 Hz), 1.56 (9H, s), 1.53 (9H, s), 1.44 (9H, s), 1.40 (3H, s), 1.27 (3H, s), 1.22 (3H, s), 1.12 (1H, td, J=8.9, 3.9 Hz), 1.06-1.01 (1H, m), 0.77 (3H, s), 0.75 (1H, d, J=11.0 Hz), 0.35 (1H, td, J=9.6, 7.1 Hz).

Reference Example 17: tert-butyl (2S,4S)-4-{3-[2-(tert-butoxycarbonyl)-3-[(tert-butoxycarbonyl)oxy]-4-{2-[(3aS,4S,6S)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}phenoxy]azetidin-1-yl}-2-carbamoylpyrrolidine-1-carboxylic acid

Reference Example 17-1: (4S)-1-(tert-butoxycarbonyl)-4-{3-[2-(tert-butoxycarbonyl)-3-[(tert-butoxycarbonyl)oxy]-4-{2-[(3aS,4S,6S)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}phenoxy]azetidin-1-yl}-L-proline

The compound of Reference Example 1-6-2 (0.145 g, 0.248 mmol) and N-tert-butoxycarbonyl-4-oxo-L-proline methyl ester (0.090 g, 0.372 mmol) were used as a raw material, and a reaction and post-processing were performed in accordance with the same method as the method described in Reference Example 3 to obtain the title compound (84.8 mg).

LCMS: [M+H]⁺/RT=797/2.072 min^(D)

Reference Example 17: tert-butyl (2S,4S)-4-{3-[2-(tert-butoxycarbonyl)-3-[(tert-butoxycarbonyl)oxy]-4-{2-[(3aS,4S,6S)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}phenoxy]azetidin-1-yl}-2-carbamoylpyrrolidine-1-carboxylic acid

HATU (0.061 g, 0.160 mmol) was added to a dichloromethane solution (1.5 mL) of the compound of Reference Example 17-1 (84.8 mg, 0.106 mmol) and N,N-diisopropylethylamine (0.093 mL, 0.532 mmol). The reaction mixture was stirred for 5 minutes at room temperature, and then ammonium chloride (0.017 g, 0.319 mmol) was added. After stirring for 2.5 hours at room temperature, an aqueous saturated ammonium chloride solution was added, and the reaction mixture was extracted with ethyl acetate. The organic layer was washed with an aqueous saturated sodium hydrogen carbonate solution followed by saturated saline, then dried with anhydrous sodium sulfate, and filtered, and the filtrate was concentrated. The resulting residue was purified by silica gel column chromatography (ethyl acetate/methanol) to obtain the title compound (31.6 mg).

LCMS: [M+H]⁺/RT=796/2.067 min^(D)

Reference Example 18: tert-butyl (2S,4S)-4-{3-[2-(tert-butoxycarbonyl)-3-[(tert-butoxycarbonyl)oxy]-4-{2-[(3aS,4S,6S)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}phenoxy]azetidin-1-yl}-2-carbamoylpyrrolidine-1-carboxylic acid

Reference Example 18-1: (4S)-1-(tert-butoxycarbonyl)-4-{3-[2-(tert-butoxycarbonyl)-3-[(tert-butoxycarbonyl)oxy]-4-{2-[(3aS,4S,6S)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}phenoxy]azetidin-1-yl}-L-proline

The compound of Reference Example 1-6-1 (100 g, 0.139 mmol) was used as a raw material, and a reaction and post-processing were performed in accordance with the same method as the method described in Reference Example 17-1 to obtain the title compound (49.2 mg) as a colorless solid.

¹H-NMR (270 MHz, CDCl₃) δ: 7.22 (1H, d, J=8.1 Hz), 6.42 (1H, d, J=8.1 Hz), 4.82-4.78 (1H, m), 4.26-4.22 (1H, m), 4.07-3.94 (3H, m), 3.65-3.60 (1H, m), 3.35-3.25 (4H, m), 2.25-1.99 (5H, m), 1.91-1.87 (1H, m), 1.80-1.74 (1H, m), 1.61-1.39 (19H, m), 1.33-1.27 (9H, m), 1.17-1.00 (6H, m), 0.94-0.83 (3H, m), 0.74 (3H, s), 0.45-0.36 (1H, m).

Reference Example 18: tert-butyl (2S,4S)-4-{3-[2-(tert-butoxycarbonyl)-3-[(tert-butoxycarbonyl)oxy]-4-{2-[(3aS,4S,6S)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}phenoxy]azetidin-1-yl}-2-carbamoylpyrrolidine-1-carboxylic acid

The compound of Reference Example 18-1 (49.2 mg, 0.0618 mmol) was dissolved in dichloromethane (1 mL), and TBTU (21.8 mg, 0.0679 mmol) and N,N-diisopropylethylamine (0.0315 mL, 0.185 mmol) were added. The reaction mixture was stirred for 15 minutes at room temperature, and ammonium (0.5 mol/L dioxane solution, 0.247 mL, 0.124 mmol) was added. The reaction mixture was stirred for 15 minutes at room temperature. A saturated sodium hydrogen carbonate solution and saturated saline were added to the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed with saturated saline, then dried with anhydrous sodium sulfate, and filtered, and the filtrate was concentrated. The resulting residue was purified by silica gel column chromatography (chloroform/methanol) to obtain the title compound (41.3 mg) as a colorless oily substance.

¹H-NMR (270 MHz, CDCl₃) δ: 7.62 (1H, br), 7.26-7.17 (2H, m), 6.41 (1H, d, J=8.1 Hz), 5.24 (1H, br), 4.71-4.67 (1H, m), 4.23-4.04 (2H, m), 3.80-3.60 (2H, m), 3.48-3.43 (1H, m), 3.33-3.27 (1H, m), 3.15-3.00 (3H, m), 2.25-1.96 (4H, m), 1.90-1.86 (1H, m), 1.79-1.73 (1H, m), 1.60-1.22 (28H, m), 1.15-0.94 (9H, m), 0.74 (3H, s), 0.44-0.35 (1H, m).

Reference Example 19: tert-butyl 6-{[1-(2-amino-2-oxoethyl)azetidin-3-yl]oxy}-2-[(tert-butoxycarbonyl)oxy]-3-{2-[(3aS,4S,6S)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}benzoate

Palladium/carbon (Pd: 10%, wetted with ca. 55% water, 20 mg) was added to a methanol (5 mL) solution of the compound of Reference Example 1-6-2 (200 mg, 0.279 mmol), and the reaction mixture was stirred for 2 hours under a hydrogen atmosphere at room temperature. The reaction mixture was filtered through celite, and the filtrate was concentrated. The resulting residue was dissolved in DMF (5 mL), and 2-iodoacetamide (77 mg, 0.418 mmol) and cesium carbonate (182 mg, 0.557 mmol) were added while cooling with ice. The reaction mixture was stirred for 1 hour at a reaction temperature of 0 to 5° C. Water was added to the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed with saturated saline, then dried with anhydrous sodium sulfate, and filtered, and the filtrate was concentrated. The resulting residue was purified by silica gel column chromatography (chloroform/methanol) to obtain the title compound (70 mg).

LCMS: [M+H]⁺/Rt=641.65/1.186 min^(H)

Reference Example 20: tert-butyl 2-[(tert-butoxycarbonyl)oxy]-6-{[1-(8,8,9,9-tetramethyl-2-oxo-4,7-dioxa-3-aza-8-siladecan-1-yl)azetidin-3-yl]oxy}-3-{2-[(3aS,4S,6S)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}benzoate

Reference Example 20-1: tert-butyl 2-[(tert-butoxycarbonyl)oxy]-6-{[1-(2-methoxy-2-oxoethyl)azetidin-3-yl]oxy}-3-{(2-[(3aS,4S,6S)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}benzoate

Triethylamine (0.049 mL, 0.352 mmol), methyl bromoacetate (0.020 mL, 0.211 mmol) and cesium carbonate (182 mg, 0.557 mmol) were added to a THF (0.7 mL) solution of the compound of Reference Example 1-7 (87.4 mg, 0.141 mmol) while cooling with ice, and the reaction mixture was stirred for 14 hours at room temperature. The reaction mixture was concentrated. The resulting residue was purified by silica gel column chromatography to obtain the title compound (33.6 mg) as a colorless oil substance.

¹H-NMR (CDCl₃) δ: 7.14 (1H, d, J=8.5 Hz), 6.40 (1H, d, J=8.5 Hz), 4.90-4.85 (1H, m), 4.17-4.12 (2H, m), 3.95-3.93 (1H, m), 3.72 (3H, s), 3.61 (1H, d, J=7.9 Hz), 3.47-3.43 (1H, m), 3.33-3.27 (1H, m), 2.15-2.07 (3H, m), 1.95-1.89 (1H, m), 1.81 (1H, t, J=5.5 Hz), 1.78-1.74 (1H, m), 1.67-1.63 (1H, m), 1.55 (9H, s), 1.52 (9H, s), 1.26 (3H, s), 1.19 (3H, s), 1.10-1.05 (1H, m), 1.03-0.98 (1H, m), 0.80 (1H, d, J=11.0 Hz), 0.72 (3H, s), 0.36 (1H, td, J=9.6, 7.1 Hz).

Reference Example 20-2: {3-[2-(tert-butoxycarbonyl)-3-[(tert-butoxycarbonyl)oxy]-4-{2-[(3aS,4S,6S)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}phenoxy]azetidin-1-yl}acetate

The compound of Reference Example 20-1 (33.6 mg, 0.051 mmol) was used as a raw material, and a reaction and post-processing were performed in accordance with the same method as the method described in Reference Example 3 to obtain the title compound (28 mg).

LCMS: [M+H]⁺/Rt=642.4/1.090 min^(B)

Reference Example 20: tert-butyl 2-[(tert-butoxycarbonyl)oxy]-6-{[1-(8,8,9,9-tetramethyl-2-oxo-4,7-dioxa-3-aza-8-siladecan-1-yl)azetidin-3-yl]oxy}-3-{2-[(3aS,4S,6S)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}benzoate

The compound of Reference Example 20-2 (28 mg, 0.044 mmol) and O-[2-{(tert-butyldimethylsilyl)oxy}ethyl]hydroxylamine hydrochloride (22 mg, 0.097 mmol) were used as a raw material, and a reaction and post-processing were performed in accordance with the same method as the method described in Reference Example 17 to obtain the title compound (45.1 mg).

LCMS: [M+H]⁺/Rt=815.49/1.26 min^(A)

Reference Example 21: tert-butyl 6-{[1-({5-[(tert-butoxycarbonyl)amino]-2,2-dimethyl-1,3-dioxa-5-yl}methyl)azetidin-3-yl]oxy}-2-[(tert-butoxycarbonyl)oxy]-3-{2-[(3aS,4S,6S)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}benzoate

Palladium/carbon (Pd: 10%, wetted with ca. 55% water, 50 mg) was added to a methanol (5 mL) solution of the compound of Reference Example 1-6-2 (0.100 g, 0.139 mmol), and the reaction mixture was stirred for 1 hour under a hydrogen atmosphere at room temperature. The reaction mixture was filtered through celite, and the filtrate was concentrated. The resulting residue was dissolved in dichloromethane (1 mL), and tert-butyl(5-formyl-2,2-dimethyl-1,3-dioxan-5-yl)carbamate (72.1 mg, 0.278 mmol) and acetic acid (0.00836 mL, 0.146 mmol) were added. The reaction mixture was stirred for 1 hour at room temperature. Sodium triacetoxyborohydride (88 mg, 0.417 mmol) was added to the reaction mixture, which was stirred at room temperature. After completion of the reaction, an aqueous saturated sodium hydrogen carbonate solution was added to the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed with saturated saline, then dried with anhydrous sodium sulfate, and filtered, and the filtrate was concentrated. The resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate) to obtain the title compound (81.4 mg).

LCMS: [M+H]⁺/RT=827/2.283 min^(D)

The compound of Reference Example 1-6-1 and aldehyde corresponding to each of the following Reference Examples were used as the starting materials, and a reaction, post-processing, and purification were performed in accordance with the same method as the method described in Reference Example 21 to obtain each of Reference Compounds 22 and 23 shown in Table 5.

TABLE 5 Reference Example Structural formula LCMS and/or NMR Reference Example 22

LCMS: [M + H]⁺/RT = 753/2.179 min^(D) Reference Example 23

LCMS: [M + H]⁺/RT = 665/1.908 min^(D)

Reference Example 24: tert-butyl 6-{[1-({(1r,4r)-4-[(tert-butoxycarbonyl) {2-[(tert-butoxycarbonyl)amino]ethyl}amino]cyclohexyl}acetyl)azetidin-3-yl]oxy}-2-[(tert-butoxycarbonyl)oxy]-3-{2-[(3aS,4S,6S)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}benzoate

Palladium/carbon (Pd: 10%, wetted with ca. 55% water, 270 mg) was added to a methanol (5 mL) solution of the compound of Reference Example 1-6-2 (0.327 g, 0.456 mmol), and the reaction mixture was stirred for 1 hour under a hydrogen atmosphere at room temperature. The reaction mixture was filtered through celite, and the filtrate was concentrated.

HATU (0.290 g, 0.762 mmol) was added to a DMF (0.8 mL) solution of 2-[(1r,4r)-4-{[(tert-butoxy)carbonyl](2-{[(tert-butoxy)carbonyl]amino}ethyl)amino}cyclohexyl]acetate (0.305 g, 0.762 mmol) and triethylamine (0.222 mL, 1.596 mmol) in a known document (e.g., J. Med. Chem. 2019, 62, 8544., etc.), and the reaction mixture was stirred for 45 minutes at room temperature. The reaction mixture was added with a DMF (1.6 mL) solution of the residue obtained from the catalytic hydrogenation reaction described above and stirred at room temperature. After 1.5 hours, an aqueous saturated ammonium chloride solution was added to the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed with an aqueous saturated sodium hydrogen carbonate solution followed by saturated saline, then dried with anhydrous sodium sulfate, and filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate) to obtain the title compound (182.2 mg).

LCMS: [M+H]⁺/RT=966/2.052 min^(E)

Reference Example 25: tert-butyl 6-[(1-{(2R)-3-[(2-aminoethyl)amino]-2-[(tert-butoxycarbonyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-2-[(tert-butoxycarbonyl)oxy]-3-{2-[(3aS,4S,6S)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}benzoate

The compound of Reference Example 14 (130 mg, 0.166 mmol) and ethylenediamine (0.017 mL, 0.248 mmol) were used as a raw material, and a reaction and post-processing were performed in accordance with the same method as the method described in Reference Example 16 to obtain the title compound (30 mg).

LCMS: [M+H]⁺/RT=419/1.167 min^(F)

1H-NMR (400 MHz, D₂O) δ: 7.06 (1H, d, J=8.5 Hz), 6.12 (1H, d, J=8.5 Hz), 3.79 (2H, m), 3.65 (1H, m), 3.55 (3H, m), 3.21 (2H, m), 3.04 (1H, d, J=12.8 Hz), 2.75 (1H, d, J=12.8 Hz), 1.84 (1H, td, J=8.0, 4.4 Hz), 1.35 (3H, s), 0.86 (1H, td, J=8.0, 2.4 Hz). 0.34 (3H, m)

Reference Example 26: tert-butyl 6-({1-[N-(tert-butoxycarbonyl)-L-histidinyl]azetidin-3-yl}oxy)-2-[(tert-butoxycarbonyl)oxy]-3-{(2-[(3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}benzoate

The compound of Reference Example 1-6-2 (100 mg, 0.139 mmol) and N^(α)-(tert-butoxycarbonyl)-L-histidine (53.4 mg, 0.209 mmol) were used as a raw material, and a reaction and post-processing were performed in accordance with the same method as the method described in Reference Example 8 to obtain the title compound (68.3 mg) as a colorless solid.

¹H-NMR (270 MHz, CDCl₃) δ: 7.21-6.90 (2H, m), 6.78-6.73 (1H, m), 6.00-5.96 (1H, m), 5.30-5.22 (1H, m), 4.73-4.63 (1H, m), 4.40-3.92 (6H, m), 3.18-2.76 (2H, m), 2.25-2.05 (3H, m), 1.99-1.95 (1H, m), 1.88-0.97 (37H, m), 0.75 (3H, s), 0.48-0.35 (1H, m).

Reference Example 27: tert-butyl 6-[(1-{2-[(tert-butoxycarbonyl)amino]ethyl}azetidin-3-yl)oxy]-2-[(tert-butoxycarbonyl)oxy]-3-{2-[(3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}benzoate

Palladium/carbon (Pd: 10%, wetted with ca. 55% water, 20 mg) and N-(tert-butoxycarbonyl)-2-aminoacetaldehyde (48.8 mg, 0.307 mmol) were added to a methanol (3 mL) solution of the compound of Reference Example 1-6-2 (200 mg, 0.279 mmol), and the reaction mixture was stirred for 4 hours under a hydrogen atmosphere at room temperature. The reaction mixture was filtered through celite, and the filtrate was concentrated. The resulting residue was purified by silica gel column chromatography (dichloromethane/methanol) to obtain the title compound (115 mg) as a colorless oily substance.

¹H-NMR (270 MHz, CDCl₃) δ: 7.15 (1H, d, J=8.1 Hz), 6.41 (1H, d, J=8.1 Hz), 4.90 (1H, br), 4.82-4.73 (1H, m), 3.98-3.94 (1H, m), 3.84-3.79 (2H, m), 3.13-3.06 (4H, m), 2.60 (2H, t, J=5.4 Hz), 2.19-2.03 (2H, m), 1.99-1.75 (2H, m), 1.70-1.21 (32H, m), 1.13-0.99 (3H, m), 0.92-0.79 (2H, m), 0.74 (3H, s), 0.42-0.33 (1H, m).

Reference Example 28: tert-butyl 5-{[(tert-butoxycarbonyl)amino]methyl}-2-(2-{3-[2-(tert-butoxycarbonyl)-3-[(tert-butoxycarbonyl)oxy]-4-{2-[(3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}phenoxy]azetidin-1-yl}-2-oxoethyl)morpholine-4-carboxylic acid

Reference Example 28-1: [4-(tert-butoxycarbonyl)-5-{[(tert-butoxycarbonyl)amino]methyl}morpholin-2-yl]acetic acid

An aqueous 2 mol/L sodium hydroxide solution (3.5 mL) and di-tert-butyl dicarbonate (0.163 mL, 0.707 mmol) were added to a THF solution (3.5 mL) of methyl 2-(5-[{(tert-butoxycarbonyl)amino}methyl]morpholin-2-yl)acetic acid (102 mg, 0.354 mmol) in a known document (e.g., Bioorg. Med. Chem. Lett., 1996, 6, 1529, etc.), and the reaction mixture was stirred for 4 hours at room temperature. Water (50 mL) and 2 mol/L hydrochloric acid (5 mL) were added to the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed with an aqueous saturated sodium hydrogen carbonate solution followed by saturated saline, then dried with anhydrous sodium sulfate, and filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (dichloromethane/methanol) to obtain the title compound (99.7 mg) as a colorless oily substance.

LCMS: [M+H]⁺/Rt=375.6/1.75 min, 375.6/1.80 min^(G) (diastereomer mixture)

1H-NMR (270 MHz, CDCl₃) δ: 4.86-4.62 (1H, m), 4.32-4.25 (1H, m), 4.14-3.97 (1H, m), 3.92-3.41 (5H, m), 3.28-3.08 (1H, m), 3.00-2.76 (1H, m), 2.66-2.45 (1H, m), 1.47-1.43 (18H, m).

Reference Example 28: tert-butyl 5-{[(tert-butoxycarbonyl)amino]methyl}-2-(2-{3-[2-(tert-butoxycarbonyl)-3-[(tert-butoxycarbonyl)oxy]-4-{2-[(3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}phenoxy]azetidin-1-yl}-2-oxoethyl)morpholine-4-carboxylic acid

Palladium/carbon (Pd: 10%, wetted with ca. 55% water, 17 mg) was added to a methanol (3 mL) solution of the compound of Reference Example 1-6-2 (170 mg, 0.237 mmol), and the reaction mixture was stirred for 30 minutes under a hydrogen atmosphere at room temperature. The reaction mixture was filtered through celite, and the filtrate was concentrated. The resulting residue was dissolved in DMF (1 mL) as solution A.

HATU (94.6 mg, 0.249 mmol) and triethylamine (0.0719 mL, 0.261 mmol) were added to a DMF solution of the compound of Reference Example 28-1 (97.6 mg, 0.261 mmol). The reaction mixture was stirred for 30 minutes at room temperature. Solution A was added, and the reaction mixture was stirred for 2 hours at room temperature. Saturated saline was added to the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed with saturated saline, then dried with anhydrous sodium sulfate, and filtered, and the filtrate was concentrated. The resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate) to obtain the title compound (150 mg) as a colorless amorphous compound.

1H-NMR (270 MHz, CDCl3) δ: 7.20-7.15 (1H, m), 6.35 (1H, d, J=8.1 Hz), 4.94-3.21 (15H, m), 2.57-2.34 (2H, m), 2.19-2.08 (2H, m), 2.01-1.92 (1H, m), 1.88-1.76 (2H, m), 1.69-0.98 (39H, m), 0.91-0.81 (6H, m), 0.74 (3H, s), 0.44-0.35 (1H, m).

Reference Example 29: Synthesis of Reference Example 1-6-2 (1 g scale)

A 1 mol/L hexane (11.4 mL, 11.4 mmol) solution of diethylzinc was dissolved in dichloromethane (8.4 mL) under a nitrogen atmosphere at −78° C., and diiodomethane (1.37 mL, 17.4 mmol) was slowly added. The reaction mixture was stirred for 5 minutes at −20° C. and then cooled again to −78° C., and a dichloromethane (4 mL) solution of the compound of Reference Example 1-4 (999 mg, 1.42 mmol) was added dropwise. The reaction mixture was stirred for 5 minutes at −78° C., then stirred for 30 minutes at −20° C., and then stirred for 22 hours at −5° C. The reaction mixture was added with a dichloromethane (2 mL) solution of di-tert-butyl dicarbonate (2.97 mL, 12.8 mmol), a dichloromethane (2 mL) solution of 4-dimethylaminopyridine (0.173 g, 1.42 mmol), and triethylamine (3.96 mL, 28.4 mmol) and stirred for 15 minutes at −5° C. and warmed to room temperature. An aqueous saturated ammonium chloride solution was added to the reaction mixture, which was extracted with chloroform. The organic layer was washed with saturated saline, then dried with anhydrous sodium sulfate, and filtered, and the filtrate was concentrated (crude product comprises a diastereomer mixture of the compound of Reference Example 1-6-1 and the compound of Reference Example 1-6-2, and the mixture ratio (1-6-1:1-6-2) was about 1:3 (according to ¹H-NMR integration ratio)). The resulting residue was purified by silica gel column chromatography to obtain the compound of Reference Example 1-6-2 (identified by TLC (silica gel plate) Rf value: 0.52 (hexane/ethyl acetate=2/1)) (473 mg) as a colorless amorphous compound. The compound of Reference Example 1-6-1 (identified by TLC (silica gel plate) Rf value: 0.46 (hexane/ethyl acetate=2/1)) was not isolated.

¹H-NMR (CDCl₃) δ: 7.35-7.27 (5H, m), 7.14 (1H, d, J=8.5 Hz), 6.31 (1H, d, J=8.5 Hz), 5.09 (2H, s), 4.92-4.86 (1H, m), 4.35-4.30 (2H, m), 4.06 (2H, dd, J=9.8, 4.3 Hz), 3.93 (1H, d, J=8.6 Hz), 2.16-2.08 (2H, m), 1.99 (2H, s), 1.94-1.90 (1H, m), 1.81 (1H, t, J=5.5 Hz), 1.77-1.74 (1H, m), 1.66-1.62 (1H, m), 1.53 (9H, s), 1.52 (9H, s), 1.25 (3H, s), 1.18 (3H, s), 1.10-1.05 (1H, m), 1.02-0.98 (1H, m), 0.80 (1H, d, J=10.4 Hz), 0.71 (3H, s), 0.39-0.32 (1H, m).

Reference Example 30: Synthesis of Reference Example 1-6-2 (4.5 g scale)

1 mol/L hexane (49.7 mL, 49.7 mmol) solution of diethylzinc was dissolved in dichloromethane (49.7 mL) under a nitrogen atmosphere at −20° C., and diiodomethane (6.88 mL, 85 mmol) was slowly added. After stirring the reaction mixture for 20 minutes at −20° C., a dichloromethane (5 mL) solution of the compound of Reference Example 1-4 (4.55 g, 6.47 mmol) was added dropwise. The reaction mixture was stirred for 30 minutes at −20° C. and then stirred for 22.5 hours at −5° C. To the reaction mixture, a dichloromethane (15 mL) solution of di-tert-butyl dicarbonate (14.85 mL, 64.0 mmol), a dichloromethane (15 mL) solution of 4-dimethylaminopyridine (0.868 g, 7.11 mmol), and triethylamine (19.8 mL, 142 mmol) were added and stirred for 30 minutes at −5° C., and then the reaction mixture was warmed to room temperature and stirred for 30 minutes. At 0° C., an aqueous saturated ammonium chloride solution was added to the reaction mixture, which was extracted with chloroform. The organic layer was washed with saturated saline, then dried with anhydrous sodium sulfate, and filtered, and the filtrate was concentrated. The resulting residue was purified by silica gel column chromatography to obtain the compound of Reference Example 1-6-2 (identified by TLC (silica gel plate) Rf value: 0.52 (hexane/ethyl acetate=2/1)) (2.537 g) as a colorless amorphous compound. The compound of Reference Example 1-6-1 (identified by TLC (silica gel plate) Rf value: 0.46 (hexane/ethyl acetate=2/1)) was not isolated.

¹H-NMR (CDCl₃) δ: 7.35-7.27 (5H, m), 7.14 (1H, d, J=8.5 Hz), 6.31 (1H, d, J=8.5 Hz), 5.09 (2H, s), 4.92-4.86 (1H, m), 4.35-4.30 (2H, m), 4.06 (2H, dd, J=9.8, 4.3 Hz), 3.93 (1H, d, J=8.6 Hz), 2.16-2.08 (2H, m), 1.99 (2H, s), 1.94-1.90 (1H, m), 1.81 (1H, t, J=5.5 Hz), 1.77-1.74 (1H, m), 1.66-1.62 (1H, m), 1.53 (9H, s), 1.52 (9H, s), 1.25 (3H, s), 1.18 (3H, s), 1.10-1.05 (1H, m), 1.02-0.98 (1H, m), 0.80 (1H, d, J=10.4 Hz), 0.71 (3H, s), 0.39-0.32 (1H, m).

Reference Example 31: (2R)-2-(2-{3-[2-(tert-butoxycarbonyl)-3-[(tert-butoxycarbonyl)oxy]-4-{2-[(3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}phenoxy]azetidin-1-yl}-2-oxoethyl)-4,4-dimethylmorpholin-4-ium iodide

Reference Example 31-1: tert-butyl (2R)-2-[2-(benzyloxy)-2-oxoethyl]morpholine-4-carboxylate

Benzylbromide (916 mg, 5.35 mmol) was added to a DMF (13.7 mL) mixture of [(2R)-4-(tert-butoxycarbonyl)morpholin-2-yl]acetic acid (1.01 g, 4.12 mmol) and cesium carbonate (2.01 g, 6.18 mmol). The reaction mixture was stirred for 3 hours at room temperature. An aqueous saturated ammonium chloride solution was added to the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed twice with an aqueous saturated ammonium chloride solution and with saturated saline, then dried with anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate) to obtain the title compound (1.33 g).

¹H-NMR (400 MHz, CDCl₃) δ: 7.37-7.28 (5H, m), 5.16 (1H, d, J=12.2 Hz), 5.11 (1H, d, J=12.2 Hz), 3.91-3.82 (4H, m), 3.54-3.48 (1H, m), 2.93-2.90 (1H, m), 2.65 (1H, brs), 2.58-2.52 (1H, m), 2.48-2.43 (1H, m), 1.44 (9H, s).

Reference Example 31-2: benzyl [(2R)-morpholin-2-yl]acetate hydrochloride

A mixture of the compound of Reference Example 31-1 (1.33 g, 3.95 mmol) and 4 mol/L hydrochloric acid/4-methyltetrahydropyran (19.8 mL, 79 mmol) was stirred at room temperature. After 2 hours, the reaction mixture was concentrated under reduced pressure to obtain the title compound (1.20 g).

¹H-NMR (400 MHz, DMSO-d₆) δ: 7.46-7.37 (5H, m), 5.20 (1H, d, J=12.2 Hz), 5.16 (1H, d, J=12.2 Hz), 4.23-4.16 (1H, m), 4.01-3.97 (1H, m), 3.83-3.76 (1H, m), 3.29 (1H, d, J=12.8 Hz), 3.21 (1H, d, J=12.8 Hz), 3.00-2.93 (1H, m), 2.90-2.77 (2H, m), 2.60-2.53 (1H, m).

Reference Example 31-3: benzyl [(2R)-4-methylmorpholin-2-yl]acetate

Diisopropylethylamine (4.14 mL, 23.70 mmol) and iodomethane (0.37 mL, 5.93 mmol) were added to a tetrahydrofuran (13 mL) mixture of the compound of Reference Example 31-2 (1.07 g, 3.95 mmol), and the reaction mixture was stirred for 6 hours at 60° C. In an ice bath, water was added to the reaction mixture, which was extracted with chloroform/ethanol (4:1). The organic layer was dried with anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (chloroform/methanol) to obtain the title compound (866.2 mg).

LCMS: [M+H]⁺/Rt=250/1.433 min^(F)

¹H-NMR (400 MHz, CDCl₃) δ: 7.36-7.27 (5H, m), 5.15 (1H, d, J=12.2 Hz), 5.10 (1H, d, J=12.2 Hz), 4.02-3.97 (1H, m), 3.86-3.83 (1H, m), 3.72-3.66 (1H, m), 2.76 (1H, d, J=11.6 Hz), 2.65 (1H, d, J=11.6 Hz), 2.59-2.53 (1H, m), 2.47-2.42 (1H, m), 2.28 (3H, s), 2.14-2.11 (1H, m), 1.91-1.86 (1H, m).

Reference Example 31-4: [(2R)-4-methylmorpholin-2-yl]acetic acid

Palladium/carbon (Pd: 10%, wetted with ca. 55% water, 540 mg) was added to a methanol (17 mL) solution of the compound of Reference Example 31-3 (838 mg, 3.36 mmol), and the reaction mixture was stirred for 1.5 hours under a hydrogen atmosphere at room temperature. The reaction mixture was filtered through celite. The filtrate was concentrated under reduced pressure to obtain the title compound (568.6 mg).

¹H-NMR (400 MHz, CD₃OD) δ: 4.03-3.92 (2H, m), 3.76-3.69 (1H, m), 3.20 (1H, d, J=12.2 Hz), 3.04 (1H, d, J=12.2 Hz), 2.63-2.56 (4H, m), 2.48-2.33 (3H, m).

Reference Example 31-5: tert-butyl 2-[(tert-butoxycarbonyl)oxy]-6-[(1-{[(2R)-4-methylmorpholin-2-yl]acetyl}azetidin-3-yl)oxy]-3-{2-[(3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}benzoate

Palladium/carbon (Pd: 10%, wetted with ca. 55% water, 618 mg) was added to a methanol (10 mL) solution of the compound of Reference Example 1-6-2 (508.5 mg, 0.709 mmol), and the reaction mixture was stirred for 1.5 hours under a hydrogen atmosphere at room temperature. The reaction mixture was filtered through celite, and the filtrate was concentrated under reduced pressure. The resulting residue was dissolved in dichloromethane (7 mL) as solution A.

1-hydroxybenzotriazole (326 mg, 2.13 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (407 mg, 2.13 mmol) were added to a dichloromethane (3 mL) mixture of the compound of Reference Example 31-4 (568.6 mg, 3.57 mmol) and diisopropylethylamine (0.619 mL, 3.54 mmol), and the reaction mixture was stirred for 30 minutes at room temperature. The reaction mixture was added with solution A described above and stirred for 3 hours at room temperature. An aqueous saturated ammonium chloride solution was then added to the reaction mixture, which was extracted with chloroform/ethanol (4:1). The organic layer was washed with an aqueous saturated sodium hydrogen carbonate solution, then dried with anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (chloroform/methanol) to obtain the title compound (258 mg).

LCMS: [M+H]⁺/Rt=725/1.692 min^(I)

Reference Example 31-5: (2R)-2-(2-{3-[2-(tert-butoxycarbonyl)-3-[(tert-butoxycarbonyl)oxy]-4-{2-[(3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}phenoxy]azetidin-1-yl}-2-oxoethyl)-4,4-dimethylmorpholin-4-ium iodide

Iodomethane (0.019 mL, 0.304 mmol) was added to a dichloromethane (0.5 mL) solution of the compound of Reference Example 31-5 (142.6 mg, 0.197 mmol). After stirring overnight at room temperature, the reaction solution was concentrated under reduced pressure to obtain the title compound (170.6 mg).

LCMS: [M+H]⁺/Rt=739/1.933 min^(D)

The compound of Reference Example 14 and amine corresponding to each of the following Reference Examples were used as a starting material, and a reaction, post-processing, and purification were performed in accordance with the same method as the method described in Reference Example 16 to obtain each of Reference Example compounds 32 and 33 shown in Table 6.

TABLE 6 Reference Example Structural formula LCMS and/or NMR 32

LCMS: [M + H]⁺/Rt = 855/1.982 min^(D) 33

LCMS: [M + H]⁺/Rt = 869/2.067 min^(D)

Reference Example 34: tert-butyl 2-[(tert-butoxycarbonyl)oxy]-6-({1-[(3-hydroxy-2-methyl-4-oxopyridin-1(4H)-yl)acetyl]azetidin-3-yl}oxy)-3-{2-[(3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}benzoate

Reference Example 34-1: tert-butyl 2-[(tert-butoxycarbonyl)oxy]-6-{[1-(chloroacetyl)azetidin-3-yl]oxy}-3-{2-[(3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}benzoate

Palladium/carbon (Pd: 10%, wetted with ca. 55% water, 150 mg) was added to a methanol (25 mL) solution of the compound of Reference Example 1-6-2 (650.0 mg, 0.906 mmol), and the reaction mixture was stirred for 4 hours under a hydrogen atmosphere at room temperature. The reaction mixture was filtered through celite, and the filtrate was concentrated under reduced pressure. The resulting residue was dissolved in chloroform (18 mL) as solution A.

Solution A was cooled with ice, and chloroacetyl chloride (133.0 mg, 1.177 mmol) and triethylamine (275 mg, 2.72 mmol) were added. The reaction mixture was then stirred for 12 hours at room temperature. Water was added to the reaction mixture, which was extracted with chloroform/ethanol (4:1). The organic layer was dried with anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate) to obtain the title compound (360 mg).

¹H-NMR (400 MHz, CDCl₃) δ: 7.16-7.08 (1H, m), 6.34-6.24 (1H, m), 4.96-4.87 (1H, m), 4.60-4.50 (1H, m), 4.40-4.33 (1H, m), 4.30-4.21 (1H, m), 4.11-4.03 (1H, m), 3.89-3.84 (1H, m), 3.82 (2H, s), 2.14-2.01 (2H, m), 1.97-1.84 (1H, m), 1.80-1.68 (1H, m), 1.65-1.55 (1H, m), 1.50 (9H, s), 1.46 (9H, s), 1.23-1.19 (3H, m), 1.14 (3H, s), 1.08-1.00 (1H, m), 0.99-0.92 (1H, m), 0.90-0.84 (1H, m), 0.81-0.74 (1H, m), 0.68 (3H, s), 0.37-0.28 (1H, m)

Reference Example 34-2: tert-butyl 6-[(1-{[3-(benzyloxy)-2-methyl-4-oxopyridin-1(4H)-yl]acetyl}azetidin-3-yl)oxy]-2-[(tert-butoxycarbonyl)oxy]-3-{2-[(3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}benzoate

A THF (15 mL) solution of 3-benzyloxy-2-methylpyridin-4-one (137 mg, 0.363 mmol) was cooled with ice, and 60% sodium hydride (27.6 mg, 0.689 mmol) was added. The reaction mixture was stirred for 20 minutes. A THF (3 mL) solution of the compound of Reference Example 34-1 (350 mg, 0.530 mmol) was added, and the reaction mixture was then stirred for 14 hours at room temperature. The reaction mixture was further heated to 60° C. and stirred for 2 hours. Water was added to the reaction mixture, which was extracted with chloroform/ethanol (4:1). The organic layer was dried with anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (ethyl acetate/methanol) to obtain the title compound (150 mg).

LCMS: [M+H]⁺/Rt=839/2.35 min^(D)

Reference Example 34: tert-butyl 2-[(tert-butoxycarbonyl)oxy]-6-({1-[(3-hydroxy-2-methyl-4-oxopyridin-1(4H)-yl)acetyl]azetidin-3-yl}oxy)-3-{2-[(3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-2H-4,6-methano-1,3,2-benzodioxaborol-2-yl]cyclopropyl}benzoate

Palladium/carbon (Pd: 10%, wetted with ca. 55% water, 35 mg) was added to a methanol (8 mL) solution of the compound of Reference Example 34-2 (150.0 mg, 0.179 mmol), and the reaction mixture was stirred for 4 hours under a hydrogen atmosphere at room temperature. The reaction mixture was filtered through celite, and the filtrate was concentrated under reduced pressure to obtain the title compound (115 mg).

LCMS: [M+H]⁺/Rt=749.54/1.289 min^(H)

Example 1: 5-({1-[amino(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid (derived from diastereomer 1-5-2; diastereo mixture)

The compound of Reference Example 1 (diastereo mixture comprising two types of diastereomer) (73.7 mg, 0.091 mmol) was dissolved in 1 mol/L hydrochloric acid/acetic acid solution (0.91 mL), and phenylboronic acid (33.4 mg, 0.274 mmol) was added. The reaction mixture was stirred for 1 hour at room temperature. The reaction mixture was concentrated. The resulting residue was washed with acetonitrile, then dissolved in methanol/water and purified by reversed phase column chromatography (column: YMC-Actus Triart C18, eluent: solution A: water, solution B: acetonitrile) to obtain the title compound (23.6 mg) as a diastereo mixture comprising two types of diastereomers.

LCMS: [M+H]⁺/Rt=399.3/0.405 min^(A)

¹H-NMR (400 MHZ, 0.02N HCl in CD₃OD) δ: 8.86 (0.5H, s), 8.84 (0.5H, s), 7.77 (0.5H, s), 7.75 (0.5H, s), 7.29 (1H, d, J=8.5 Hz), 6.41 (0.5H, dd, J=8.5, 1.8 Hz), 6.38 (0.5H, d, J=8.5 Hz), 5.52 (0.5H, s), 5.46 (0.5H, d, J=1.8 Hz), 5.13-5.09 (0.5H, m), 5.03-4.99 (0.5H, m), 4.70-4.65 (0.5H, m), 4.54 (0.5H, dd, J=11.0, 6.7 Hz), 4.44 (0.5H, dd, J=11.0, 6.7 Hz), 4.33-4.28 (0.5H, m), 4.25-4.20 (0.5H, m), 4.14-4.09 (0.5H, m), 4.07-4.02 (0.5H, m), 3.76-3.71 (0.5H, m), 2.26-2.21 (1H, m), 1.34-1.28 (1H, m), 0.58-0.52 (1H, m), 0.32-0.25 (1H, m).

The compound of Example 1, which is a diastereo mixture, was separated into the first peak (Rt=3.465 min) and the second peak (Rt=4.491 min) by the following chiral chromatography. Accordingly, each of two types of diastereomers contained in the compound of Example 1 can be further fractionated and identified.

Column: CROWNPAK CR-I(+) (0.30 cmI.D.×15 cmL) (Daicel Corporation)

Mobile phase: aqueous perchloric acid solution (pH 1.0)/acetonitrile (85/15<v/v>)

Flow rate: 0.5 mL/min

Temperature: 25° C.

Example 2: 5-({1-[amino(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid (derived from diastereomer 1-5-1; diastereo mixture)

The compound of Reference Example 2 (diastereo mixture comprising two types of diastereomers) (82.5 mg, 0.102 mmol) was used as a raw material, and a reaction and post-processing were performed in accordance with the same method as the method described in Example 1 to obtain the title compound (25.1 mg) as a diastereo mixture comprising two types of diastereomers.

LCMS: [M+H]⁺/Rt=399.14/0.413 min^(A)

¹H-NMR (400 MHZ, D₂O) δ: 7.49-7.47 (1H, m), 7.05 (0.5H, s), 7.03 (0.5H, s), 6.82 (0.51H, d, J=8.5 Hz), 6.81 (0.5H, d, J=8.5 Hz), 5.90 (0.5H, d, J=8.5 Hz), 5.90 (0.5H, d, J=8.5 Hz), 4.95 (0.5H, s), 4.94 (0.5H, s), 4.69-4.64 (0.5H, m), 4.58-4.53 (0.5H, m), 4.21-4.11 (1H, m), 4.08-4.04 (0.5H, m), 3.87-3.83 (0.5H, m), 3.79-3.71 (1H, m), 3.60-3.56 (0.5H, m), 3.29-3.25 (0.5H, m), 1.86-1.81 (1H, m), 0.91-0.86 (1H, m), 0.19-0.12 (1H, m), 0.02-0.02 (1H, m).

The compound of Example 2, which is a diastereomer mixture, was separated into the first peak (Rt=3.446 min) and the second peak (Rt=4.508 min) by the following chiral chromatography. Accordingly, each of two types of diastereomers contained in the compound of Example 2 can be further fractionated and identified.

Column: CROWNPAK CR-I(+) (0.30 cmI.D.×15 cmL) (Daicel Corporation)

Mobile phase: aqueous perchloric acid solution (pH 1.0)/acetonitrile (85/15<v/v>)

Flow rate: 0.5 mL/min

Temperature: 25° C.

The compound of Example 1 and the compound of Example 2 are diastereo mixtures comprising two types of diastereomers that are different from each other, collectively consisting of four different diastereomers A1 to A4 shown in the following Table. They can be prepared separately or fractionated through chiral chromatography as described above. Specifically, the four types of diastereomers were substantially synthesized. A1 and A2 or A3 and A4 always form a pair to constitute a diastereo mixture of either Example 1 or Example 2. If Example 1 is a mixture consisting of one of the pairs, Example 2 is a mixture consisting of the other pair.

[Chemical Formula 707] Serial Chemical structure of diastereomer number [abbreviation based on configuration] Chemical name A1

(1aS,7bR)-5-({1-[(2R)-2-amino-2-(1H-imidazol-4- yl)acetyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b- tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid A2

(1aS,7bR)-5-({l-[(2S)-2-amino-2-(1H-imidazol-4- yl)acetyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b- tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid A3

(1aR,7bS)-5-({1-[(2R)-2-amino-2-(1H-imidazol-4- yl)acetyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b- tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid A4

(1aR,7bS)-5-({1-[(2S)-2-amino-2-(1H-imidazol-4- yl)acetyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b- tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

Example 3: 9-[1-(propyl 2-amino-2-carboxylate) azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7), 8,10-triene-8-carboxylate trisodium salt (derived from diastereomer 1-5-1; single diastereomer

An aqueous 6 mol/L hydrochloric acid solution (0.085 mL) and phenylboronic acid (2.9 mg, 0.024 mmol) were added to a cyclopentyl methyl ether solution (0.127 mL) of the compound of Reference Example 3 (20 mg, 0.025 mmol), and the reaction mixture was stirred for 14 hours at room temperature. The supernatant solution of the reaction solution was removed, and the remaining solid was washed three times by decantation with cyclopentyl methyl ether. The resulting residue was added with an aqueous 2 mol/l sodium hydroxide solution (0.064 mL, 0.127 mmol) and purified by reversed phase column chromatography (Column: YMC-Actus Triart C18, eluent: solution A: water, solution B: acetonitrile) to obtain the title compound (4.9 mg) as a single diastereomer.

LCMS: [M+H]⁺/Rt=377.15/0.369 min^(A)

¹H-NMR (400 MHZ, D₂O) δ: 7.00 (1H, d, J=8.7 Hz), 6.10 (1H, d, J=8.2 Hz), 4.73-4.67 (1H, m), 3.77 (2H, q, J=7.3 Hz), 3.32-3.24 (2H, m), 2.90 (1H, d, J=12.5 Hz), 2.65 (1H, d, J=12.5 Hz), 1.80-1.75 (1H, m), 1.16 (3H, s), 0.81-0.76 (1H, m), 0.28-0.25 (1H, m), 0.20 (1H, td, J=9.1, 6.4 Hz).

The compound of Example 3 is a single diastereomer, which is one of the two types of different diastereomers B1 and B2 shown in the following table. The other isomer can also be synthesized in the same manner as Reference Example 3 and Example 3 by using the compound of Reference Example 1-6-2 instead of the compound of Reference Example 1-6-1 in Reference Example 3-1.

[Chemical Formula 709] Serial Chemical structure of diastereomer number [abbreviation based on configuration] Chemical name B1

(2R,4S)-9-[1-[propyl(2R)-2-amino-2-carboxylate]azetidin-3-yl]oxy- 5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca- 1(7),8,10-triene-8-carboxylate trisodium salt B2

(2S,4R)-9-[1-[propyl(2R)-2-amino-2-carboxylate]azetidin-3-yl]oxy- 5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca- 1(7),8,10-triene-8-carboxylate trisodium salt

Example 4: 5-({1-[2-amino-2-(1H-imidazol-4-yl)propanoyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid (derived from diastereomer 1-5-2; diastereo mixture)

The compound of Reference Example 4 (diastereo mixture comprising two types of diastereomers) (13.5 mg, 0.016 mmol) was dissolved in a 1 mol/L hydrochloric acid/acetic acid solution (0.32 mL), and phenylboronic acid (6.2 mg, 0.051 mmol) was added. The reaction mixture was stirred for 3 hours at room temperature. The reaction mixture was concentrated. The resulting residue was washed with acetonitrile, then dissolved in triethylamine (0.01 mL)/water (0.5 mL) and purified by reversed phase column chromatography (Column: YMC-Actus Triart C18, eluent: solution A: water, solution B: acetonitrile). The eluent was lyophilized after adding triethylamine (0.01 mL) to obtain the title compound (6.5 mg) as a diastereo mixture comprising two types of diastereomers and a triethylamine containing substance.

LCMS: [M+H]⁺/Rt=413.17/0.423 min^(A)

¹H-NMR (400 MHZ, CD₃OD) δ: 7.81 (0.5H, s), 7.78 (0.5H, s), 7.35 (0.5H, s) 7.33 (0.5H, s), 7.09 (1H, d, J=8.5 Hz), 6.06-6.03 (1H, m), 4.79-4.76 (1H, m), 4.40-4.27 (2H, m), 4.10-3.98 (2H, m), 1.92-1.85 (1H, m), 1.84 (3H, s), 0.97-0.93 (1H, m), 0.37-0.32 (2H, m).

Example 5: 5-({1-[2-amino-2-(1H-imidazol-4-yl)propanoyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid (derived from diastereomer 1-5-1; diastereo mixture)

The compound of Reference Example 5 (diastereo mixture comprising two types of diastereomers) (11.8 mg, 0.014 mmol) was used as a raw material, and a reaction and post-processing were performed in accordance with the same method as the method described in Example 4 to obtain the title compound (4.7 mg) as a diastereo mixture comprising two types of diastereomers and a triethylamine containing substance (containing about 0.3 mol ratio of triethylamine with respect to the compound of Reference Example 5 according to NMR integration ratio).

LCMS: [M+H]⁺/Rt=413.24/0.435 min^(A)

¹H-NMR (400 MHZ, CD₃OD) δ: 7.81 (0.5H, s), 7.78 (0.5H, s), 7.34 (0.5H, s), 7.31 (0.5H, s), 7.08 (1H, d, J=8.5 Hz), 6.05-6.02 (1H, m), 4.80-4.75 (1H, m), 4.40-4.26 (2H, m), 4.07-4.00 (2H, m), 1.92-1.85 (1H, m), 1.83 (3H, s), 0.99-0.92 (1H, m), 0.38-0.31 (2H, m).

The compound of Example 4 and the compound of Example 5 are diastereo mixtures comprising two types of diastereomers that are different from each other, collectively consisting of four different diastereomers C1 to C4 shown in the following Table. They can be prepared separately or fractionated through chiral chromatography as described above. Specifically, the four types of diastereomers were substantially synthesized. C1 and C2 or C3 and C4 always form a pair to constitute a diastereo mixture of either Example 4 or Example 5. If Example 4 is a mixture consisting of one of the pairs, Example 5 is a mixture consisting of the other pair.

[Chemical Formula 712] Serial Chemical structure of diastereomer number [abbreviation based on configuration] Chemical name C1

(1aS,7bR)-5-({1-[(2R)-2-amino-2-(1H-imidazol-4- yl)propanoyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b- tetrahydrocyclopropa[c][l,2]benzoxaborinine-4-carboxylic acid C2

(1aS,7bR)-5-({1-[(2S)-2-amino-2-(1H-imidazol-4- yl)propanoyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b- tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid C3

(1aR,7bS)-5-({1-[(2R)-2-amino-2-(1H-imidazol-4- yl)propanoyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b- tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid C4

(1aR,7bS)-5-({1-[(2S)-2-amino-2-(1H-imidazol-4- yl)propanoyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b- tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

The compounds of Reference Examples (R)-6 and (S)-6 were used as a raw material, and reaction, post-processing, and purification were performed in accordance with the same method as the method described in Example 1 to obtain the following Example compounds 6 and 7.

TABLE 7 Raw Example Material Structural formula NMR and/or LCMS 6 Reference Example (R)-6

¹H-NMR (D₂O) δ: 7.50 (1H, br s), 7.02 (1H, br s), 6.75 (1H, d, J = 8.5 Hz), 5.77 (1H, d, J = 8.5 Hz), 4.74-4.69 (1H, m), 4.65-4.60 (1H, m), 4.34-4.25 (0.5H, m), 4.22-4.15 (0.5H, m), 4.14-4.08 (0.5H, m), 4.01-3.95 (0.5H, m), 3.88-3.83 (1H, m), 3.81-3.75 (0.5H, m), 3.60-3.51 (0.5H, m), 1.56-1.51 (1H, m), 0.58-0.53 (1H, m), 0.01-0.07 (2H, m). (rotamer) 7 Reference Example (S)-6

¹H-NMR (D₂O) δ: 7.50-7.47 (1H, m), 7.07-7.03 (1H, m), 6.81 (0.5 H, d, J = 8.5 Hz), 6.80 (0.5H, d, J = 8.5 Hz), 5.89 (0.5H, d, J = 8.5 Hz), 5.88 (0.5H, d, J = 8.5 Hz), 4.96-4.94 (1H, m), 4.69-4.65 (0.5H, m), 4.59-4.55 (0.5H, m), 4.21-4.12 (1H, m), 4.09-4.04 (0.5H, m), 3.90-3.85 (0.5H, m), 3.80-3.73 (1H, m), 3.62-3.57 (0.5H, m), 3.31- 3.27 (0.5H, m), 1.82-1.76 (1H, m), 0.86-0.80 (1H, m), 0.16-0.09 (1H, m), 0.02-0.02 (1H, m). (rotamer)

The column retention times of the compound of Example 6 and the compound of Example 7 in chiral chromatography were the following.

Column: CROWNPAK CR-I(−) (0.30 cmI.D.×15 cmL) (Daicel Corporation)

Mobile phase: solution A/solution B=85/15

Solution A: aqueous perchloric acid solution (70% perchloric acid/water=1/100 VV)

Solution B: acetonitrile

Flow rate: 0.5 mL/min

Temperature: 25° C.

Rt of compound of Example 6: 6.300 min

Rt of compound of Example 7: 4.235 min

Optical purity of Example 6 (computed by HPLC area percentage value): 99.3% ee

Optical purity of Example 7 (computed by HPLC area percentage value): 97.8% ee

The compound of Example 6 is a single diastereomer, which is one of the two types of different diastereomers 6A and 6B shown in the following table. The other isomer can also be synthesized in the same manner as Reference Example 1, Reference Example (R)-6, and Example 6 by using the compound of Reference Example 1-6-1 instead of the compound of Reference Example 1-6-2 in Reference Example 1-7.

[Chemical Formula 713] Serial Chemical structure of diastereomer number [abbreviation based on configuration] Chemical name 6A

(1aS,7bR)-5-({1-[(2R)-2-amino-2-(1H-imidazol-4-yl)acetyl]azetidin- 3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2] benzoxaborinine-4-carboxylic acid 6B

(1aR,7bS)-5-({1-[(2R)-2-amino-2-(1H-imidazol-4-yl)acetyl]azetidin- 3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2] benzoxaborinine-4-carboxylic acid

The compound of Example 7 is a single diastereomer, which is one of the two types of different diastereomers 7A and 7B shown in the following table. The other isomer can also be synthesized in the same manner as Reference Example 1, Reference Example (S)-6, and Example 7 by using the compound of Reference Example 1-6-1 instead of the compound of Reference Example 1-6-2 in Reference Example 1-7.

[Chemical Formula 714] Serial Chemical structure of diastereomer number [abbreviation based on configuration] Chemical name 7A

(1aS,7bR)-5-({1-[(2S)-2-amino-2-(1H-imidazol-4-yl)acetyl]azetidin- 3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2] benzoxaborinine-4-carboxylic acid 7B

(1aR,7bS)-5-({1-[(2S)-2-amino-2-(1H-imidazol-4-yl)acetyl]azetidin- 3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2] benzoxaborinine-4-carboxylic acid

Example 8: 5,5-dihydroxy-9-{1-[(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid disodium salt

The compound of Reference Example 7 (110 mg, 0.159 mmol) was dissolved in a 1 mol/L hydrochloric acid/acetic acid solution (1.59 mL) while cooling with ice, and phenylboronic acid (58 mg, 0.477 mmol) was added. After stirring for 2 hours at room temperature, reaction mixture was concentrated. The resulting residue was washed with acetonitrile and then dissolved in water (2 mL). An aqueous 2 mol/L sodium hydroxide solution (0.318 mL) was added while cooling with ice. The reaction mixture was purified by reversed phase column chromatography (Column: YMC-Actus Triart C18, solution A: water, solution B: acetonitrile) and lyophilized to obtain the title compound (46 mg).

¹H-NMR (D₂O) δ: 7.73 (1H, s), 7.05 (1H, d, J=8.6 Hz), 6.11 (1H, d, J=8.6 Hz), 5.04-4.94 (1H, m), 4.63-4.59 (1H, m), 4.43-4.38 (1H, m), 4.33-4.28 (1H, m), 4.10-4.05 (1H, m), 3.36 (2H, s), 1.84-1.78 (1H, m), 0.84-0.79 (1H, m), 0.31-0.21 (2H, m)

The compound of Example 8 is a single diastereomer, which is one of the two types of different diastereomers 8A and 8B shown in the following table. The other isomer can also be synthesized in the same manner as Reference Example 7 and Example 8 by using the compound of Reference Example 1-6-1 instead of the compound of Reference Example 1-6-2 in Reference Example 7.

[Chemical Formula 716] Serial Chemical structure of diastereomer number [abbreviation based on configuration] Chemical name 8A

(2R,4S)-5,5-dihydroxy-9-{1-[(1H-imidazol-4-yl)acetyl]azetidin- 3-yl}oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9- triene-8-carboxylic acid disodium salt 8B

(2S,4R)-5,5-dihydroxy-9-{1-[(1H-imidazol-4-yl)acetyl]azetidin- 3-yl}oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9- triene-8-carboxylic acid disodium salt

The compounds of Reference Example 10 to 13 were used as a raw material, and a reaction, post-processing, and purification were performed in accordance with the same method as the method described in Example 8 to obtain the following Example compounds 9 to 12.

TABLE 8 Example Raw material Structural formula NMR and/or LCMS  9 Reference Example 10

¹H-NMR (D2O) δ: 7.73 (1H, brs), 7.05 (1H, d, J = 8.0 Hz), 6.12 (1H, d, J = 8.0 Hz), 5.09-5.00 (1H, m), 4.69-4.61 (1H, m), 4.47-4.29 (2H, m), 4.12-4.07 (1H, m), 3.36-3.29 (1H, m), 3.17-3.09 (1H, m), 2.34- 2.26 (1H, m), 2.09-2.02 (1H, m), 1.91-1.79 (1H, m), 0.85-0.80 (1H, m), 0.31-0.20 (2H, m) 10 Reference Example 11

LCMS: [M + H]⁺/RT = 377.17/0.305 min^(B) ¹H-NMR (D2O) δ: 6.81 (1H, d, J = 8.5 Hz), 5.87 (1H, d, J = 8.5 Hz), 4.79-4.74 (1H, m), 4.67-4.61 (1H, m), 4.33-4.28 (1H, m), 4.20-4.14 (1H, m), 3.88-3.82 (1H, m), 3.57 (1H, dd, J = 11.6, 7.3 Hz), 3.30 (1H, dd, J = 11.9, 3.4 Hz), 1.57 (1H, td, J = 8.2, 3.9 Hz), 1.09 (3H, s), 0.60-0.55 (1H, m), 0.07-0.04 (2H, m). 11 Reference Example 12

LCMS: [M + H]⁺/RT = 403.21/0.338 min^(B) ¹H-NMR (D₂O) δ: 6.81 (1H, d, J = 8.5 Hz), 5.88 (0.5H, d, J = 8.5 Hz), 5.88 (0.5H, d, J = 8.5 Hz), 4.80- 4.73 (1H, m), 4.40-4.34 (1H, m), 4.17-4.11 (1H, m), 4.09-4.04 (1H, m), 3.84-3.72 (3H, m), 3.54-3.47 (1H, m), 2.93-2.88 (1H, m), 2.86-2.81 (1H, m), 2.73 (1H, t, J = 12.2 Hz), 2.55 (1H, t, J = 11.9 Hz), 2.27- 2.12 (2H, m), 1.60-1.54 (1H, m), 0.60-0.55 (1H, m), 0.07-0.05 (2H, m). (rotamer) 12 Reference Example 13

¹H-NMR (D₂O) δ: 6.82-6.80 (1H, m), 5.86 (1H, d, J = 15.5), 4.81-4.72 (1H, m), 4.42-4.34 (1H, m), 4.19-4.01 (2H, m), 3.86-3.77 (1H, m), 3.73-3.60 (2H, m), 3.47-3.35 (1H, m), 2.76-2.67 (1H, m), 2.66-2.50 (2H, m), 2.41-2.31 (1H, m), 2.24-2.06 (2H, m), 1.61-1.53 (1H, m), 0.62-0.54 (1H, m), 0.08-0.05 (2H, m)

The compounds of Examples 9 to 12 are single diastereomers, which are one of the two types of different diastereomers shown in the following table. The other isomer can also be synthesized in the same manner as the corresponding Reference Example and Example by using the compound of Reference Example 1-6-1 instead of the compound of Reference Example 1-6-2 in Reference Examples 10 to 13.

Serial Chemical structure of diastereomer Example number [abbreviation based on configuration] Chemical name [Chemical Formula 717-1] 9 9A

(2R,4S)-5_(;)5-dihydroxy-9-{1-[(4R)-4-hydroxy-L- prolyl]azetidin-3-yl}oxy-6-oxa-5- boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene- 8-carboxylic acid disodium salt 9B

(2S,4R)-5,5-dihydroxy-9-{1-[(4R)-4-hydroxy-L- prolyl]azetidin-3-yl}oxy-6-oxa-5- boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9- triene-8-carboxylic acid disodium salt 10 10A

(2R,4S)-5,5-dihydroxy-9-[1-(2-methyl-D-seryl)azetidin-3-yl]oxy-6-oxa-5- boranuidatricyclo[5.4.0.0^(2,4)]undeca- 1(11),7,9-triene-8-carboxylic acid disodium salt 10B

(2S,4R)-5,5-dihydroxy-9-[1-(2-methyl-D-seryl)azetidin-3-yl]oxy-6-oxa-5- boranuidatricyclo[5.4.0.0^(2,4)]undeca- 1(11),7,9-triene-8-carboxylic acid disodium salt [Chemical Formula 717-2] 11 11A

(2R,4S)-5,5-dihydroxy-9-(1-{[(2R)-morpholin-2- yl]acetyl}azetidin-3-yl)oxy-5- boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9- triene-8-carboxylic acid disodium salt 11B

(2S,4R)-5,5-dihydroxy-9-(1-{[(2R)-morpholin-2- yl]acetyl}azetidin-3-yl)oxy-5- boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9- triene-8-carboxylic acid disodium salt 12 12A

(2R,4S)-5_(;)5-dihydroxy-9-(1-{[(2S)-morpholin-2- yl]acetyl}azetidin-3-yl)oxy-5- boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9- triene-8-carboxylic acid disodium salt 12B

(2S,4R)-5,5-dihydroxy-9-(1-{[(2R)-morpholin-2- yl]acetyl}azetidin-3-yl)oxy-5- boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene- 8-carboxylic acid disodium salt

Example 13: 2-hydroxy-5-[(1-D-serylazetidin-3-yl)oxy]-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

Phenylboronic acid (16.8 mg, 0.138 mmol), hexane (2 mL), and 4 mol/L hydrochloric acid/cyclopentyl methyl ether solution (1.09 mL) were added to an acetonitrile solution (1 mL) of the compound of Reference Example 8 (112 mg, 0.145 mmol), and the reaction mixture was stirred for 3.5 hours at room temperature. After leaving the reaction mixture standing, the supernatant (top layer) from the reaction mixture separated into two layers was removed, and the remaining bottom layer was washed with hexane (the washing step removes the supernatant after leaving the reaction mixture standing). The bottom layer was concentrated, and the resulting residual was purified by reversed phase column chromatography (Column: YMC-Actus Triart C18, solution A: water, solution B: acetonitrile) and lyophilized. Acetonitrile (1 mL) was added to the resulting residue. A solid was filtered out and dried under reduced pressure to obtain the title compound (7.0 mg) as a white solid.

LCMS: [M+H]⁺/Rt=363.2/0.75 min^(G)

¹H-NMR (270 MHz, D2O) δ: 7.00 (1H, d, J=8.1 Hz), 6.07 (1H, d, J=8.1 Hz), 5.00-4.59 (2H, m), 4.42-4.28 (2H, m), 4.06-4.00 (1H, m), 3.68-3.56 (3H, m), 1.80-1.70 (1H, m), 0.80-0.73 (1H, m), 0.21-0.16 (2H, m).

The compound of Example 13 is a single diastereomer, which is one of the two types of different diastereomers 13A and 13B shown in the following table. The other isomer can also be synthesized in the same manner as Reference Example 8 and Example 13 by using the compound of Reference Example 1-6-2 instead of the compound of Reference Example 1-6-1 in Reference Example 8.

[Chemical Formula 719] Serial Chemical structure of diastereomer number [abbreviation based on configuration] Chemical name 13A

(1aS,7bR)-2-hydroxy-5-[(1-D-serylazetidin-3-yl)oxy]- 1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine- 4-carboxylic acid 13B

(1aR,7bS)-2-hydroxy-5-[(1-D-serylazetidin-3-yl)oxy]- 1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

Example 14: 5,5-dihydroxy-9-{1-[(4R)-4-hydroxy-L-prolyl]azetidin-3-yl}oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid disodium salt

Phenylboronic acid (6.5 mg, 0.054 mmol) and a 4 mol/L hydrochloric acid/cyclopentyl methyl ether solution (0.424 mL) were added to an acetic acid solution (0.56 mL) of the compound of Reference Example 8 (45 mg, 0.056 mmol), and the reaction mixture was stirred for 2 hours at room temperature. After leaving the reaction mixture standing, the supernatant (top layer) from the reaction mixture separated into two layers was removed, and the remaining bottom layer was washed with hexane (the washing step removes the supernatant after leaving the reaction mixture standing). The bottom layer was concentrated. The resulting residue was washed with acetonitrile, and an aqueous 2 mol/L sodium hydroxide solution (0.1 mL) was added while cooling with ice. The reaction mixture was purified by reversed phase column chromatography (Column: YMC-Actus Triart C18, solution A: water, solution B: acetonitrile) and lyophilized to obtain the title compound (8.2 mg).

LCMS: [M+H]⁺/Rt=389.4/0.88 min^(G)

¹H-NMR (270 MHz, D2O) δ: 7.02 (1H, d, J=8.1 Hz), 6.10-6.06 (1H, m), 5.08-4.96 (1H, m), 4.65-4.55 (2H, m), 4.44-4.02 (4H, m), 3.31-3.22 (1H, m), 3.08-2.99 (1H, m), 2.27-2.17 (1H, m), 2.04-1.93 (1H, m), 1.82-1.75 (1H, m), 0.82 (1H, t. J=8.1 Hz), 0.28-0.15 (2H, m).

The compound of Example 14 is a single diastereomer, which is one of the two types of different diastereomers 14A and 14B shown in the following table. The other isomer can also be synthesized in the same manner as Reference Example 9 and Example 14 by using the compound of Reference Example 1-6-2 instead of the compound of Reference Example 1-6-1 in Reference Example 9.

[Chemical Formula 721] Serial Chemical structure of diastereomer number [abbreviation based on configuration] Chemical name 14A

(2R,4S)-5,5-dihydroxy-9-{1-[(4R)-4-hydroxy-L-prolyl]azetidin- 3-yl}oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9- triene-8-carboxylic acid disodium salt 14B

(2S,4R)-5,5-dihydroxy-9-{1-[(4R)-4-hydroxy-L-prolyl]azetidin- 3-yl}oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9- triene-8-carboxylic acid disodium salt

Example 15: 9-[1-[propyl (2R)-2-amino-2-carboxylate]azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic acid trisodium salt

The compound of Reference Example 14 (108.8 mg, 0.139 mmol) was dissolved in 1 mol/L hydrochloric acid/acetic acid solution (2 mL), and phenylboronic acid (51 mg, 0.416 mmol) and water (0.2 mL) were added. The reaction mixture was stirred for 4 hours at room temperature. Cyclopentyl methyl ether was added to the reaction mixture. After leaving the reaction mixture standing, the supernatant (top layer) from the reaction mixture separated into two layers was removed, and the remaining bottom layer was washed with cyclopentyl methyl ether (the washing step removes the supernatant after leaving the reaction mixture standing). The bottom layer was concentrated. The resulting residue was washed with acetonitrile, and an aqueous 4 mol/L sodium hydroxide solution (0.174 mL) was added while cooling with ice. The reaction mixture was purified by reversed phase column chromatography (Column: YMC-Actus Triart C18, solution A: water, solution B: acetonitrile) and lyophilized to obtain the title compound (18.9 mg).

¹H-NMR (D₂O) δ: 6.85 (1H, d, J=8.5 Hz), 5.94 (1H, d, J=8.5 Hz), 4.61-4.58 (1H, m), 3.70-3.66 (2H, m), 3.30-3.24 (2H, m), 2.93 (1H, d, J=13.4 Hz), 2.69 (1H, d, J=13.4 Hz), 1.65-1.60 (1H, m), 1.22 (3H, s), 0.66-0.61 (1H, m), 0.13-0.02 (2H, m).

The compound of Example 15 is a single diastereomer, which is one of the two types of different diastereomers 15A and 15B shown in the following table. The other isomer can also be synthesized in the same manner as Reference Example 14 and Example 15 by using the compound of Reference Example 1-6-1 instead of the compound of Reference Example 1-6-2 in Reference Example 14.

[Chemical Formula 723] Serial Chemical structure of diastereomer number [abbreviation based on configuration] Chemical name 15A

(2R,4S)-9-[1-[propyl (2R)-2-amino-2-carboxylate]azetidin-3- yl]oxy-5,5-dihydroxy-6-oxa-5- boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8- carboxylic acid trisodium salt 15B

(2S,4R)-9-[1-[propyl (2R)-2-amino-2-carboxylate]azetidin-3- yl]oxy-5,5-dihydroxy-6-oxa-5- boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8- carboxylic acid trisodium salt

Example 16: 9-{1-[2-amino-3-hydroxy-2-(hydroxymethyl)propyl]azetidin-3-yl}oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic acid disodium salt

The compound of Reference Example 21 (81.4 mg, 0.098 mmol) was used as a raw material, and a reaction, post-processing, and purification were performed in accordance with the same method as the method described in Example 15 to obtain the title compound (21.8 mg).

¹H-NMR (D₂O) δ: 6.86 (1H, d, J=7.9 Hz), 5.95 (1H, d, J=7.9 Hz), 4.67-4.63 (1H, m), 3.74 (2H, brs), 3.61-3.21 (8H, m), 1.65-1.61 (1H, m), 0.65-0.63 (1H, m), 0.32-0.00 (2H, m).

The compound of Example 16 is a single diastereomer, which is one of the two types of different diastereomers 16A and 16B shown in the following table. The other isomer can also be synthesized in the same manner as Reference Example 21 and Example 16 by using the compound of Reference Example 1-6-1 instead of the compound of Reference Example 1-6-2 in Reference Example 21.

[Chemical Formula 725] Serial Chemical structure of diastereomer number [abbreviation based on configuration] Chemical name 16A

(2R,4S)-9-{1-[2-amino-3-hydroxy-2- (hydroxymethyl)propyl]azetidin-3-yl}oxy-5,5- dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8- carboxylic acid disodium salt 16B

(2S,4R)-9-{1-[2-amino-3-hydroxy-2- (hydroxymethyl)propyl]azetidin-3-yl}oxy-5,5- dihydroxy-6-oxa-5- boranuidatricyclo[5.4.0.0^(2,4)]ndeca- 1(7),8,10-triene-8- carboxylic acid disodium salt

Example 17: 9-(1-{(2R)-2-amino-3-[(2-hydroxyethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic acid disodium salt

The compound of Reference Example 15 (37.6 mg, 0.045 mmol) was dissolved in a 1 mol/L hydrochloric acid/acetic acid solution (0.454 mL), and phenylboronic acid (5.7 mg, 0.047 mmol) and water (0.02 mL) were added. The reaction mixture was stirred for 1.5 hours at room temperature. The reaction mixture was concentrated. The resulting residue was washed with cyclopentyl methyl ether, and then an aqueous 2 mol/L sodium hydroxide solution (0.091 mL) was added while cooling with ice. The reaction mixture was purified by reversed phase column chromatography (Column: YMC-Actus Triart C18, solution A: water, solution B: acetonitrile) and lyophilized to obtain the title compound (6.4 mg).

LCMS: [M+H]⁺/RT=420.20/0.425 min^(A)

¹H-NMR (D₂O) δ: 6.86 (1H, d, J=7.9 Hz), 5.94 (1H, d, J=7.9 Hz), 4.60-4.54 (1H, m), 3.64-3.58 (2H, m), 3.53 (2H, t, J=5.5 Hz), 3.23-3.15 (4H, m), 2.83 (1H, d, J=12.9 Hz), 2.55 (1H, d, J=12.9 Hz), 1.63 (1H, td, J=8.2, 3.7 Hz), 1.09 (3H, s), 0.67-0.62 (1H, m), 0.14-0.03 (2H, m).

The compound of Example 17 is a single diastereomer, which is one of the two types of different diastereomers 17A and 17B shown in the following table. The other isomer can also be synthesized in the same manner as Reference Examples 14 and 15 and Example 17 by using the compound of Reference Example 1-6-1 instead of the compound of Reference Example 1-6-2 in Reference Example 14.

[Chemical Formula 727] Serial Chemical structure of diastereomer number [abbreviation based on configuration] Chemical name 17A

(2R,4S)-9-(1-{(2R)-2-amino-3- [(2-hydroxyethyl)amino]- 2-methyl-3-oxopropyl}azetidin-3-yl)oxy-5,5- dihydroxy-6-oxa-5- boranuidatricyclo[5.4.0.0^(2,4)]undeca- 1(7),8,10-triene-8-carboxylic acid disodium salt 17B

(2S,4R)-9-(1-{(2R)-2-amino-3- [(2-hydroxyethyl)amino]- 2-methyl-3-oxopropyl}azetidin-3-yl)oxy-5,5- dihydroxy-6-oxa-5- boranuidatricyclo[5.4.0.0^(2,4)]undeca- 1(7),8,10-triene-8-carboxylic acid disodium salt

Example 18: 9-(1-{(2R)-2-amino-3-[(2-amino-2-oxoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic acid disodium salt

Water (0.678 mL), trifluoroacetic acid (6.8 mL, 89 mmol), and triethylsilane (0.341 mL, 2.13 mmol) were added to a mixture of the compound of Reference Example 16 (299.1 mg, 0.356 mmol) and phenylboronic acid (130 mg, 1.067 mmol) while cooling with ice, and the reaction mixture was stirred for 2 hours at room temperature. Cyclopentyl methyl ether and water were added to the reaction mixture while cooling with ice. After leaving the reaction mixture, the supernatant (top layer) from the reaction mixture separated into two layers was removed, and the remaining bottom layer was washed with cyclopentyl methyl ether (the washing step removes the supernatant after leaving the reaction mixture standing). The bottom layer was concentrated, and the resulting residual was washed with acetonitrile, and then an aqueous 2 mol/L sodium hydroxide solution (0.89 mL) was added while cooling with ice. The reaction mixture was purified by reversed phase column chromatography (Column: YMC-Actus Triart C18, solution A: water, solution B: acetonitrile) and lyophilized to obtain the title compound (6.4 mg).

¹H-NMR (D₂O) δ: 6.87 (1H, d, J=8.5 Hz), 5.94 (1H, d, J=8.5 Hz), 4.61-4.57 (1H, m), 3.79 (2H, s), 3.67-3.59 (2H, m), 3.26-3.22 (2H, m), 2.84 (1H, d, J=12.8 Hz), 2.60 (1H, d, J=12.8 Hz), 1.67-1.62 (1H, m), 1.13 (3H, s), 0.69-0.63 (1H, m), 0.15-0.02 (2H, m).

The compound of Example 18 is a single diastereomer, which is one of the two types of different diastereomers 18A and 18B shown in the following table. The other isomer can also be synthesized in the same manner as Reference Examples 14 and 16 and Example 18 by using the compound of Reference Example 1-6-1 instead of the compound of Reference Example 1-6-2 in Reference Example 14.

[Chemical Formula 729] Serial Chemical structure of diastereomer number [abbreviation based on configuration] Chemical name 18A

(2R,4S)-9-(1-{(2R)-2-amino-3- [(2-amino-2-oxoethyl)amino]-2- methyl-3-oxopropyl}azetidin-3-yl)oxy- 5,5-dihydroxy-6-oxa-5- boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10- triene-8-carboxylic acid disodium salt 18B

(2S,4R)-9-(1-{(2R)-2-amino-3- [(2-amino-2-oxoethyl)amino]- 2-methyl-3-oxopropyl}azetidin-3-yl)oxy- 5,5-dihydroxy-6-oxa- 5-boranuidatricyclo[5.4.0.0^(2,4)]undeca- 1(7),8,10-triene-8-carboxylic acid disodium salt

The compounds of Reference Examples 17, 18, and 22 to 25 were used as a raw material, and a reaction, post-processing, and purification were performed in accordance with the same method as the method described in Example 18 to obtain the following Example compounds 19 to 24.

TABLE 9 Exam- Raw ple Material Structural formula NMR and/or LCMS [1] 19 Refer- ence Exam- ple 17

¹H-NMR (D2O) δ: 7.01 (1H, d, J = 8.5 Hz), 6.12 (1H, d, J = 8.5 Hz), 4.83-4.73 (1H, m), 3.82-3.70 (3H, m), 3.37-3.24 (3H, m), 3.08- 3.02 (1H, m), 2.76-2.72 (1H, m), 2.53-2.39 (1H, m), 1.81-1.75 (1H, m), 1.71- 1.50 (1H, m), 0.82-0.77 (1H, m), 0.29-0.17 (2H, m). 20 Refer- ence Exam- ple 18

LCMS: [M+H]⁺/Rt = 388.3/0.38 min^(G) ¹H-NMR (270 MHz, D2O) δ: 6.99 (1H, d, J = 8.1 Hz), 6.00 (1H, d, J = 8.1 Hz), 4.89-4.71 (1H, m), 3.82-3.76 (3H, m), 3.39-3.25 (3H,m), 3.06-3.00 (1H, m), 2.76-2.70 (1H, m), 2.46-2.35 (1H, m), 1.80-1.72 (1H, m), 1.58- 1.47 (1H, m), 0.76 (1H, t. J = 8.1 Hz), 0.27-0.14 (2H, m). 21 Refer- ence Exam- ple 22

¹H-NMR (D2O) δ: 7.05 (1H, d, J = 7.9 Hz), 6.13 (1H, d, J = 7.9 Hz), 4.95-4.88 (1H, m), 4.10-4.06 (2H, m), 3.69-3.64 (2H, m), 2.87 (2H, s), 1.83-1.78 (1H, m), 0.84-0.79 (1H, m), 0.69-0.62 (4H, m), 0.32-0.18 (2H, m). 22 Refer- ence Exam- ple 23

¹H-NMR (D2O) δ: 8.36 (1H, s), 7.04 (1H, d, J = 8.5 Hz), 6.13 (1H, d, J = 8.5 Hz), 4.88-4.83 (2H, m), 4.06 (2H, s), 4.02-3.98 (2H, m), 3.63-3.62 (2H, m), 1.86-1.81 (1H, m), 0.86-0.83 (1H, m), 0.30-0.26 (2H, m). [2] 23 Refer- ence Exam- ple 24

¹H-NMR (D2O) δ: 7.04 (1H, d, J = 8.5 Hz), 6.10 (1H, d, J = 8.5 Hz), 5.00-4.96 (1H, m), 4.61-4.57 (1H, m), 4.39-4.35 (1H, m), 4.27-4.25 (1H, m), 4.04-3.99 (1H, m), 3.33-2.87 (5H, m), 2.17-2.03 (4H, m), 1.87-1.78 (3H, m), 1.71-1.65 (1H, m),1.42-1.24 (2H, m), 1.17-1.04 (2H, m), 0.84-0.79 (1H, m), 0.29-0.19 (2H, m). 24 Refer- ence Exam- ple 25

LCMS: [M+H]⁺/RT = 419.10/1.167 min^(F) ¹H-NMR (400 MHz, D2O) δ: 7.06 (1H, d, J = 8.5 Hz), 6.12 (1H, d, J = 8.5 Hz), 3.79 (2H, m), 3.65 (1H, m), 3.55 (3H, m), 3.21 (2H, m), 3.04 (1H, d, J = 12.8 Hz), 2.75 (1H, d, J = 12.8 Hz), 1.84 (1H, td, J = 8.0, 4.4 Hz), 1.35 (3H, s), 0.86 (1H, td, J = 8.0, 2.4 Hz). 0.34 (3H, m)

The compounds of Examples 19 to 24 are single diastereomers, which are one of the two types of different diastereomers shown in the following table. The other isomer can also be synthesized in the same manner as a corresponding Reference Example and an Example by using the compound of Reference Example 1-6-1 instead of the compound of Reference Example 1-6-2 in Reference Examples 17 and 22 to 25, or by using the compound of Reference Example 1-6-2 instead of the compound of Reference Example 1-6-1 in Reference Example 18.

Serial Chemical structure of diastereomer Example number [abbreviation based on configuration] Chemical name [Chemical Formula 730-1] 19 and 20 D1

(2R,4S)-9-{1-[(3S,5S)-5-carbamoylpyrrolidin- 3-yl]azetidin-3-yl}oxy-5,5-dihydroxy-6-oxa-5- boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10- triene-8-carboxylic acid disodium salt D2

(2S,4R)-9-{1-[(3S_(;)5S)-5-carbamoylpyrrolidin- 3-yl]azetidin-3-yl}oxy-5,5-dihydroxy-6-oxa-5- boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10- triene-8-carboxylic acid disodium salt 21 21A

(2R,4S)-9-{1-[(1-aminocyclopropyl)methyl]azetidin- 3-yl}oxy-5,5-dihydroxy-6-oxa-5- boranuidatricyclo[5.4.0.0^(2,4)]undeca- 1(7),8,10-triene-8- carboxylic acid disodium salt 21B

(2S,4R)-9-{1-[(1- aminocyclopropyl)methyl]azetidin-3-yl}oxy- 5,5-dihydroxy-6-oxa-5- boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10- triene-8-carboxylic acid disodium salt [Chemical Formula 730-2] 22 22A

(2R,4S)-5,5-dihydroxy-9-{1- [(1H-1,2,4-triazol-3- yl)methyl]azetidin-3-yl}oxy-5- boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9- triene-8-carboxylic acid disodium salt 22B

(2S,4R)-5,5-dihydroxy-9-{1-[(1H-1,2,4-triazol-3- yl)methyl]azetidin-3-yl}oxy-5- boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9- triene-8-carboxylic acid disodium salt 23 23A

(2R_(/)4S)-9-[1-({(1r,4r)-4-[(2- aminoethyl)amino]cyclohexyl}acetyl)azetidin- 3-yl]oxy-5,5-dihydroxy-6-oxa-5- boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10- triene-8-carboxylic acid disodium salt 23B

(2S,4R)-9-[1-({(1r,4r)-4-[(2- aminoethyl)amino]cyclohexyl}acetyl)azetidin- 3-yl]oxy-5,5-dihydroxy-6-oxa-5- boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10- triene-8-carboxylic acid disodium salt [Chemical Formula 730-3] 24 24A

(2R,4S)-9-(1-{(2R)-2-amino-3-[(2- aminoethyl)amino]-2-methyl-3- oxopropyl}azetidin-3-yl)oxy-5,5-dihydroxy-6- oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca- 1(7),8,10-triene-8-carboxylic acid disodium salt 24B

(2S,4R)-9-(1-{(2R)-2-amino-3-[(2- aminoethyl)amino]-2-methyl-3- oxopropyl}azetidin-3-yl)oxy-5,5-dihydroxy-6- oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca- 1(7),8,10-triene-8-carboxylic acid disodium salt

The compounds of Reference Examples 19, 20, and 26 to 28 were used as a raw material, and a reaction, post-processing, and purification were performed in accordance with the same method as the method described in Example 13 to obtain the following Example compounds 25 to 29.

TABLE 10 Raw Structural Example Material formula NMR and/or LCMS [1] 25 Reference Example 19

LCMS: [M+H]⁺/RT = 333.22/0.356 min^(H) 26 Reference Example 20

¹H-NMR (D2O) δ: 6.95 (1H, d, J = 8.5 Hz), 6.04 (1H, d, J = 8.5 Hz), 4.77 (1H, t, J = 5.5 Hz), 3.94-3.90 (2H, m), 3.87 (2H, t, J = 4.6 Hz), 3.70-3.68 (2H, m), 3.52-3.46 (2H, m), 3.22 (2H, s), 1.74-1.69 (1H, m), 0.75-0.70 (1H, m), 0.22-0.19 (1H, m), 0.17-0.09 (1H, m). 27 Reference Example 26

LCMS: [M+H]⁺/Rt = 413.6/0.31min^(G) ¹H-NMR (270 MHz, D2O) δ: 7.71-7.45 (1H, m), 7.03-6.99 (1H, m), 6.95-6.91 (1H, m), 6.03-5.88 (1H, m), 4.89-4.70 (1H, m), 4.43-4.14 (2H, m), 4.04-2.99 (3H, m), 2.91-2.72 (2H, m), 1.83-1.76 (1H, m), 0.84-0.78 (1H, m), 0.31-0.17 (2H, m). 28 Reference Example 27

LCMS: [M+H]+/Rt = 319.4/0.30min^(G) ¹H-NMR (270 MHz, D2O) δ: 7.02 (1H, d, J = 8.1 Hz), 6.14 (1H, d, J = 8.1 Hz), 4.90-4.70 (1H, m), 3.76-3.71 (2H, m), 3.29-3.23 (2H, m), 2.69-2.58 (4H, m), 1.83- 1.75 (1H, m), 0.80 (1H, t, J = 8.1 Hz), 0.30-0.17 (2H, m). [2] 29 Reference Example 28

LCMS: [M+H]+/Rt = 432.5/0.43min^(G) ¹H-NMR (270 MHz, D2O) δ: 7.05 (1H, d, J = 8.1 Hz), 6.11 (1H, d, J = 8.1 Hz), 5.04-4.96 (1H, m), 4.65-4.58 (1H, m), 4.41-4.27 (2H, m), 4.06-3.24 (4H, m), 2.98-2.30 (7H, m), 1.84-1.76 (1H, m), 0.81 (1H, t, J = 8.1 Hz), 0.31-0.13 (2H, m).

The compounds of Examples 25 to 29 are single diastereomers, which are one of the two types of different diastereomers shown in the following table. The other isomer can also be synthesized in the same manner as a corresponding Reference Example and an Example by using the compound of Reference Example 1-6-1 instead of the compound of Reference Example 1-6-2 in Reference Examples 19, 20, and 26 to 28.

Example Serial Chemical structure of diastereomer number [abbreviation based on configuration] Chemical name [Chemical Formula 731-1] 25 25A

(2R,4S)-9-[1-(2-amino-2- oxoethyl)azetidin-3-yl]oxy- 5,5-dihydroxy-6-oxa-5- boranuidatricyclo[5.4.0.0^(2,4)]undeca- 1(7),8,10-triene- 8-carboxylic acid disodium salt 25B

(2S,4R)-9-[1-(2-amino-2- oxoethyl)azetidin-3-yl]oxy- 5,5-dihydroxy-6-oxa-5- boranuidatricyclo[5.4.0.0^(2,4)]undeca- 1(7),8,10-triene- 8-carboxylic acid disodium salt 26 26A

(2R,4S)-5,5-dihydroxy-9-(1-{2-[(2- hydroxyethoxy)amino]-2- oxoethyl}azetidin-3-yl)oxy-5- boranuidatricyclo[5.4.0.0^(2,4)]undeca- 1(11),7,9- triene-8-carboxylic acid disodium salt 26B

(2S,4R)-5_(/)5-dihydroxy-9-(1-{2-[(2- hydroxyethoxy)amino]-2- oxoethyl}azetidin-3-yl)oxy-5- boranuidatricyclo[5.4.0.0^(2,4)]undeca- 1(11),7,9- triene-8-carboxylic acid disodium salt [Chemical Formula 731-2] 27 27A

(2R,4S)-9-(1-L- histidylazetidin-3yl)oxy-5,5- dihydroxy-6-oxa-5- boranuidatricyclo[5.4.0.0^(2,4)]undeca- 1(7),8,10- triene-8-carboxylic acid disodium salt 27B

(2S,4R)-9-(1-L- histidylazetidin-3-yl)oxy-5,5- dihydroxy-6-oxa-5- boranuidatricyclo[5.4.0.0^(2,4)]undeca- 1(7),8,10- triene-8-carboxylic acid disodium salt 28 28A

(2R,4S)-9-[1-(2-aminoethyl)azetidin- 3-yl]oxy-5,5-dihydroxy-6-oxa-5- boranuidatricyclo[5.4.0.0^(2,4)]undeca- 1(7),8,10- triene-8-carboxylic acid disodium salt 28B

(2S,4R)-9-[1-(2-aminoethyl)azetidin- 3-yl]oxy-5,5- dihydroxy-6-oxa-5- boranuidatricyclo[5.4.0.02^(2,4)]undeca- 1(7),8,10- triene-8-carboxylic acid disodium salt [Chemical Formula 731-3] 29 29A

(2R,4S)-9-(1- {[5-(aminomethyl)morpholin-2- yl]acetyl}azetidin-3-yl)oxy-5,5- dihydroxy-6-oxa-5- boranuidatricyclo[5.4.0.0^(2,4)]undeca- 1(7),8,10- triene-8-carboxylic acid disodium salt 29B

(2S,4R)-9-(1- {[5-(aminomethyl)morpholin-2- yl]acetyl}azetidin-3-yl)oxy-5,5- dihydroxy-6-oxa-5- boranuidatricyclo[5.4.0.0^(2,4)]undeca- 1(7),8,10- triene-8-carboxylic acid disodium salt

The compounds of Reference Examples 31 to 34 were used as a raw material, and a reaction, post-processing, and purification were performed in accordance with the same method as the method described in Example 18 to obtain the following Example compounds 30 to 34.

TABLE 11 Example Raw Material Structural formula NMR and/or LCMS [1] 30 Reference Example 31

¹H-NMR (400 MHz, D₂O) δ: 6.89 (1H, d, J = 8.5 Hz), 5.97-5.94 (1H, m), 4.87-4.82 (1H, m), 4.47-4.42 (1H, m), 4.28-4.21 (2H, m), 4.17-4.11 (1H, m), 3.97-3.87 (3H, m), 3.41-3.33 (3H, m), 3.20-3.16 (1H, m), 3.13 (3H, s), 3.10 (3H, s), 2.41-2.24 (2H, m), 1.67-1.62 (1H, m), 0.68-0.63 (1H, m), 0.14-0.01 (2H, m). 31 Reference Example 32

¹H-NMR (400 MHz, D₂O) δ: 6.85 (1H, d, J = 8.5 Hz), 5.92 (1H, d, J = 8.5 Hz), 4.62-4.56 (1H, m), 3.73 (2H, s), 3.65-3.58 (2H, m), 3.21-3.17 (2H, m), 2.83 (1H, d, J = 13.4 Hz), 2.59- 2.55 (4H, m), 1.65-1.60 (1H, m), 1.10 (3H, s), 0.66-0.61 (1H, m), 0.13-0.02 (2H, m). 32 Reference Example 33

¹H-NMR (400 MHz, D₂O) δ: 6.85 (1H, d, J = 8.5 Hz), 5.94 (1H, d, J = 8.5 Hz), 4.60-4.55 (1H, m), 4.00- 3.90 (2H, m), 3.65-3.58 (2H, m), 3.18-3.15 (2H, m), 2.91 (3H, s), 2.83 (1H, d, J = 13.4 Hz), 2.80 (3H, s), 2.57 (1H, d, J = 13.4 Hz), 1.65-1.60 (1H, m), 1.11 (3H, s), 0.66-0.61 (1H, m), 0.13-0.00 (2H, m). [2] 33 Reference Example 31-5

¹H-NMR (400 MHz, D₂O) δ: 6.82 (1H, d, J = 8.0 Hz), 5.88 (1H, d, J = 8.4 Hz), 4.78-4.71 (1H, m), 4.38 (1H, m), 4.14 (1H, m), 4.07 (1H, m), 3.81 (1H, m), 3.68 (2H, m), 3.40 (1H, m), 2.06 (1H, d, J = 13.6 Hz), 2.52 (1H, d, J = 11.2 Hz), 2.19 (1H, m), 2.03 (3H, s), 1.78(2H, m), 1.68 (1H, m), 0.57 (1H, m), 0.05-0.01 (2H, m). 34

LCMS: [M+H]⁺/Rt = 441.3/0.584 min^(H) ¹H-NMR (400 MHz, D₂O) δ: 7.38-7.27 (1H, m), 6.87-6.78 (1H, m), 6.33-6.24 (1H, m), 5.93-5.84 (1H, m), 4.90-4.81 (1H, m), 4.74-4.66 (2H, s), 4.49-4.37 (1H, m), 4.29-4.21 (1H, m), 4.20-4.08 (1H, m), 3.97-3.86 (1H, m), 2.12-2.02 (3H, s), 1.62-1.51 (1H, m), 0.62- 0.52 (1H, m), 0.09-0.04 (2H, m)

The compounds of Examples 30 to 34 are single diastereomers, which are one of the two types of different diastereomers shown in the following table. The other isomer can also be synthesized in the same manner as a corresponding Reference Example and an Example by using the compound of Reference Example 1-6-1 instead of the compound of Reference Example 1-6-2 in Reference Examples 31 to 34.

Serial Chemical structure of diastereomer Example number [abbreviation based on configuration] Chemical name [Chemical Formula 732-1] 30 30A

(2R,4S)-9-[1-[2-[(2R)-4,4- dimethylmorpholin4-ium- 2-yl]acetyl]azetidin-3-yl]oxy-5,5- dihydroxy-6-oxa-5- boranuidatricyclo[5.4.0.0^(2,4)]undeca- 1(7),8,10- triene-8-carboxylate hydroxide disodium salt 30B

(2S,4R)-9-[1-[2-[(2R)-4,4- dimethylmorpholin-4-ium- 2-yl]acetyl]azetidin-3-yl]oxy-5,5- dihydroxy-6-oxa-5- boranuidatricyclo[5.4.0.0^(2,4)]undeca- 1(7),8,10- triene-8-carboxylate hydroxide disodium salt 31 31A

(2R,4S)-9-[1-[(2R)-2-amino- 2-methyl-3-[[2- (methylamino)-2- oxoethyl]amino]-3- oxopropyl]azetidin-3-yl]oxy-5,5- dihydroxy-6-oxa-5- boranuidatricyclo[5.4.0.0^(2,4)]undeca- 1(7),8,10-triene-8- carboxylate disodium salt [Chemical Formula 732-2] 31B

(2S,4R)-9-[1-[(2R)-2-amino-2- methyl-3-[[2-(methylamino)- 2-oxoethyl]amino]-3- oxopropyl]azetidin-3-yl]oxy- 5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca- 1(7),8,10-triene-8- carboxylate disodium salt 32 32A

(2R,4S)-9-[1-[(2R)-2-amino-3-[[2- (dimethylamino)-2-oxoethyl]amino]- 2-methyl- 3-oxopropyl]azetidin-3- yl]oxy-5,5-dihydroxy-6- oxa-5- boranuidatricyclo[5.4.0.0²'⁴]undeca- 1(7),8,10-triene-8- carboxylate disodium salt 32B

(2S,4R)-9-[1-[(2R)-2-amino-3-[[2- (dimethylamino)-2-oxoethyl]amino]- 2-methyl-3-oxopropyl]azetidin- 3-yl]oxy-5,5-dihydroxy-6-oxa-5- boranuidatricyclo[5.4.0.0^(2,4)]undeca- 1(7),8,10-triene-8- carboxylate disodium salt [Chemical Formula 732-3] 33 33A

(2R,4S)-5,5-dihydroxy-9- [(1-{[(2R)-4- methylmorpholin-2- yl]acetyl}azetidin-3- yl)oxy]-5- boranuidatricyclo[5.4.0.0″f]undeca- 1(11),7,9-triene-8- carboxylic acid disodium salt 33B

(2S,4R)-5,5-dihydroxy-9-[(1-{[(2R)-4- methylmorpholin-2-yl]acetyl}azetidin-3- yl)oxy]-5- boranuidatricyclo[5.4.0.0^(2,4)]undeca- 1(11),7,9-triene-8- carboxylic acid disodium salt 34 34A

(2R,4S)-5,5-dihydroxy-9- ({1-[(3-hydroxy-2- methyl-4-oxopyridin- 1(4H)-yl)acetyl]azetidin- 3-yl}oxy)-5- boranuidatricyclo[5.4.0.0²'⁴]undeca- 1(11),7,9- triene-8-carboxylic acid disodium salt 34B

(2S,4R)-5,5-dihydroxy-9- ({1-[(3-hydroxy-2- methyl-4-oxopyridin- 1(4H)-yl)acetyl]azetidin- 3-yl}oxy)-5- boranuidatricyclo[5.4.0.0²'⁴]undeca- 1(11),7,9- triene-8-carboxylic acid disodium salt

Test Example 1

To evaluate the β-lactamase inhibitory activity of test compounds evaluated for the minimum inhibitory concentration (MIC) of MEPM against β-lactamase producing bacteria, the effect of concomitant use of the test compound and a β-lactam agent against β-lactamase producing bacteria was evaluated. Meropenem (MEPM) was used as a β-lactam antimicrobial agent. The minimum inhibitory concentration (MIC) of MEPM against β-lactamase producing bacteria when a test compound was added at a fixed concentration (4 μg/mL) was measured by broth microdilution method (common ratio: 2).

The numerical values of (MIC of MEPM in combination with a test compound)/(MIC of MEPM alone) are shown below.

Pharmacological testing methods and results thereof for representative compounds of the invention are shown hereinafter, but the present invention is not limited to the Test Examples.

Test Example 1: Evaluation of Minimum Inhibitory Concentration (MIC) of MEPM Against β-Lactamase Producing Bacteria

To evaluate the β-lactamase inhibitory activity of test compounds, the effect of combination of a test compound and a β-lactam agent against β-lactamase producing bacteria was evaluated. Meropenem (MEPM) was used as a β-lactam antimicrobial agent. The minimum inhibitory concentration (MIC) of MEPM against β-lactamase producing bacteria when a test compound was added at a fixed concentration (4 μg/mL) was measured by broth microdilution method (common ratio: 2).

The numerical values of (MIC of MEPM in combination with a test compound)/(MIC of MEPM alone) are shown below.

TABLE 3 K. pneumoniae K. pneumoniae Example ATCC BAA-2344 ATCC BAA-2524 number (KPC) (OXA-48) 1 ≤0.063/32  ≤0.063/2  2 0.125/32 ≤0.063/2  3 ≤0.063/32  ≤0.063/2  4 ≤0.063/32  ≤0.063/2  5 ≤0.063/32  ≤0.063/2  6 0.031/32 0.063/2 7 0.031/32 0.063/2 8 0.031/32 0.031/2 9 0.031/32 0.063/2 10 0.031/32 0.063/2 11 0.031/32 0.063/2 12 0.125/32 0.031/1 13 0.031/32 0.031/2 14 0.031/32 0.031/2 15 0.031/32 0.031/2 16 0.031/32 0.031/2 17 0.031/32 0.031/1 18 0.063/32 0.063/2 19 0.031/32 0.031/2 20 0.031/32 0.031/2 21 0.031/32 0.031/2 22 0.031/32 0.031/2 23  0.25/32 0.031/2 24 0.031/32 0.063/1 25 0.063/32 0.063/2 26 0.031/32 0.063/2 27 0.031/32 0.031/2 28 0.031/32 0.031/1 29 0.063/32 0.031/2 30 0.031/32 0.031/2 31 0.031/32 0.031/2 32 0.031/32 0.031/2 33 0.031/32 0.031/2

Test Example 2: Evaluation of Minimum Inhibitory Concentration (MIC) of MEPM Against β-Lactamase Producing Bacteria

In the same manner as Test Example 1, E. coli ATCC BAA-2340 (KPC), E. coli ATCC BAA-2469 (NDM-1), K. pneumoniae ATCC BAA-2470 (NDM-1), K. pneumoniae NCTC 13439 (VIM-1), K. pneumoniae NCTC 13440 (VIM-1), E. coli NCTC 13476 (IMP), and the like can be used to evaluate metallo-β-lactamase inhibitory activity of test compounds.

As disclosed above, the present invention is exemplified by the use of its preferred embodiments. However, it is understood that the scope of the present invention should be interpreted based solely on the Claims. The present application claims priority to Japanese Patent Application No. 2019-194753 (filed on Oct. 25, 2019). The entire content thereof is incorporated herein by reference. It is also understood that any patent, any patent application, and any other references cited herein should be incorporated herein by reference in the same manner as the contents are specifically described herein.

INDUSTRIAL APPLICABILITY

The compound of the invention exhibits a potent inhibitory action against β-lactamase and is useful as a therapeutic agent and/or prophylactic agent for sepsis, febrile neutropenia, bacterial meningitis, bacterial endocarditis, otitis media, sinusitis, pneumonia, lung abscess, empyema, secondary infection of a chronic respiratory disease, pharyngolaryngitis, tonsillitis, osteomyelitis, arthritis, peritonitis, intraperitoneal abscess, cholecystitis, cholangitis, liver abscess, deep skin infection, lymphangitis/lymphadenitis, secondary infection of trauma, burn injury, surgical wound, or the like, urinary tract infection, genital infection, eye infection, or odontogenic infection. 

1. A compound represented by formula (1a) or (1b):

or a pharmaceutically acceptable salt thereof wherein G is an oxygen atom, a sulfur atom, or —NR^(a1)—, X is a hydroxyl group, an optionally substituted alkoxy group, or —NR^(a2)R^(b1), R^(a1), R^(a2), and R^(b1) are the same or different, each independently a hydrogen atom, a hydroxyl group, an optionally substituted hydrocarbyl group, or an optionally substituted heterohydrocarbyl group, wherein R^(2a) and R^(b1) together may form an optionally substituted nitrogen-containing non-aryl heterocycle, L¹ is a single bond, an oxygen atom, a sulfur atom, —SO—, —SO₂—, an optionally substituted hydrocarbylene group, or an optionally substituted heterohydrocarbylene group, L² is a single bond or an optionally substituted hydrocarbylene group, Z is a hydrogen atom, a hydroxyl group, an optionally substituted hydrocarbyl group, or an optionally substituted heterohydrocarbyl group, one of R¹, R², and R³ is represented by formula (2):

wherein Y is an oxygen atom, a sulfur atom, or —NR^(j)—, and R^(j) is a hydrogen atom, a hydroxyl group, or an optionally substituted hydrocarbyl group, ring A is an optionally substituted non-aryl heterocycle, L³ is an oxygen atom, a sulfur atom, an optionally substituted hydrocarbylene group, an optionally substituted heterohydrocarbylene group, optionally substituted —NH—, optionally substituted —NH—SO₂—, —S(═O)—, or —S(═O)₂—, L⁴ is a single bond, an optionally substituted hydrocarbylene group, an optionally substituted heterohydrocarbylene group, or —C(═N—OR^(h1))—, R^(h1) is 1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₁₀ alicyclic group, 4) C₆₋₁₀ aryl, 5) 5- or 6-membered heteroaryl, or 6) a 4- to 10-membered non-aryl heterocycle, (wherein each substituent from 2) to 6) is optionally substituted), R⁵ is a hydrogen atom, a hydroxyl group, an optionally substituted hydrocarbyl group, an optionally substituted heterohydrocarbyl group, optionally substituted —NHOH, a sulfo group (sulfonic acid group), optionally substituted —SO₂H, optionally substituted —SO₂—NH₂, optionally substituted —S(═O)(═NH)H, optionally substituted —NH—SO₂—H, optionally substituted —NH—SO₂—NH₂, optionally substituted —N═S(═O)H₂, or optionally substituted —NH₂, the remaining two (without the structure of formula (2) among R¹, R², and R³) are the same or different, each independently a hydrogen atom, halogen, a hydroxyl group, an optionally substituted hydrocarbyl group, or an optionally substituted heterohydrocarbyl group, R⁴ is 1) —C(═O)R⁸, 2) —SO₂-L⁶-R⁸, (wherein R⁸ in 1) and 2) is a hydroxyl group, an optionally substituted hydrocarbyl group, or an optionally substituted heterohydrocarbyl group, and L⁶ is a single bond or an optionally substituted hydrocarbylene group), 3) —NR^(a4)R^(b3), 4) —B(OR^(m1))₂, 5) —PO(OR^(m1))(OR^(m2)), 6) optionally substituted heteroaryl, 7) an optionally substituted non-aryl heterocycle, or 8) a bioisostere of one of 1) to 7), (wherein the formulas of 1), 2), 4), 5), and 6) include a carboxylic acid isostere, and 8) may include them in duplicates), R^(a4) and R^(b3) are the same or different, each independently having the same definition as R^(a1), R^(a2), and R^(b1), wherein a combination of R^(a4) and R^(b3), when attached to the same nitrogen atom, together may form an optionally substituted nitrogen-containing non-aryl heterocycle, R^(m1) is a hydrogen atom or an optionally substituted hydrocarbyl group, wherein if R^(m1) is attached to a boron atom via an oxygen atom, two R^(m1), as alkylene, together with the boron atom and two oxygen atoms, may form a non-aryl heterocycle (wherein an alkylene moiety is optionally substituted in the non-aryl heterocycle), R^(m2) is a hydrogen atom or an optionally substituted hydrocarbyl group, and R⁶¹, R⁶², R⁶³, and R⁶⁴ are each independently a hydrogen atom, halogen, an optionally substituted alkyl group, or -L¹-L²-Z.
 2. A compound represented by formula (1a) or (1b):

or a pharmaceutically acceptable salt thereof wherein G is an oxygen atom, a sulfur atom, or —NR^(a1)—, X is a hydroxyl group, an optionally substituted alkoxy group, or —NR^(a2)R^(b1), R^(a1), R^(a2), and R^(b1) are the same or different, each independently a hydrogen atom, a hydroxyl group, an optionally substituted hydrocarbyl group, or an optionally substituted heterohydrocarbyl group, wherein R^(a2) and R^(b1) together may form an optionally substituted nitrogen-containing non-aryl heterocycle, L¹ is a single bond, an oxygen atom, a sulfur atom, —SO—, —SO₂—, an optionally substituted hydrocarbylene group, or an optionally substituted heterohydrocarbylene group, L² is a single bond or an optionally substituted hydrocarbylene group, Z is a hydrogen atom, a hydroxyl group, an optionally substituted hydrocarbyl group, or an optionally substituted heterohydrocarbyl group, one of R¹, R², and R³ is represented by formula (2):

wherein Y is an oxygen atom, a sulfur atom, or —NR^(j)—, and R^(j) is a hydrogen atom, a hydroxyl group, or an optionally substituted hydrocarbyl group, ring A is an optionally substituted non-aryl heterocycle, L³ is an oxygen atom, a sulfur atom, an optionally substituted hydrocarbylene group, an optionally substituted heterohydrocarbylene group, —S(═O)—, or —S(═O)₂—, L⁴ is a single bond, an optionally substituted hydrocarbylene group, or —C(═N—OR^(h1))—, R^(h1) is 1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₁₀ alicyclic group, 4) C₆₋₁₀ aryl, 5) 5- or 6-membered heteroaryl, or 6) a 4- to 10-membered non-aryl heterocycle, (wherein each substituent from 2) to 6) is optionally substituted), R⁵ is a hydrogen atom, a hydroxyl group, an optionally substituted hydrocarbyl group, or an optionally substituted heterohydrocarbyl group, the remaining two (without the structure of formula (2) among R¹, R², and R³) are the same or different, each independently a hydrogen atom, halogen, a hydroxyl group, an optionally substituted hydrocarbyl group, or an optionally substituted heterohydrocarbyl group, R⁴ is 1) —C(═O)R⁸, 2) —SO₂-L⁶-R⁸, (wherein R⁸ in 1) and 2) is a hydroxyl group, an optionally substituted hydrocarbyl group, or an optionally substituted heterohydrocarbyl group, and L⁶ is a single bond or an optionally substituted hydrocarbylene, 3) —NR^(a4)R^(b3), 4) —B(OR^(m1))₂, 5) —PO(OR^(m1))(OR^(m2)), 6) optionally substituted heteroaryl, 7) an optionally substituted non-aryl heterocycle, or 8) a bioisostere of one of 1) to 7), (wherein the formulas of 1), 2), 4), 5), and 6) include a carboxylic acid isostere, and 8) may include them in duplicates), R^(a4) and R^(b3) are the same or different, each independently having the same definition as R^(a1), R^(a2), and R^(b1), wherein a combination of R^(a4) and R^(b3), when attached to the same nitrogen atom, together may form an optionally substituted nitrogen-containing non-aryl heterocycle, R^(m1) is a hydrogen atom or an optionally substituted hydrocarbyl group, wherein if R^(m1) is attached to a boron atom via an oxygen atom, two R^(m1), as alkylene, together with the boron atom and two oxygen atoms, may form a non-aryl heterocycle (wherein an alkylene moiety is optionally substituted in the non-aryl heterocycle), R^(m2) is a hydrogen atom or an optionally substituted hydrocarbyl group, and R⁶¹, R⁶², R⁶³, and R⁶⁴ are each independently a hydrogen atom, halogen, an optionally substituted alkyl group, or -L¹-L²-Z.
 3. The compound or the pharmaceutically acceptable salt thereof according to claim 1 or 2, represented by formula (1a) or (1b):

wherein G is an oxygen atom, a sulfur atom, or —NR^(a1)—, X is a hydroxyl group, an optionally substituted C₁₋₆ alkoxy group, or —NR^(a2)R^(b1), R^(a1), R^(a2), and R^(b1) are the same or different, each independently 1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₁₀ alicyclic group, 4) C₆₋₁₀ aryl, 5) 5- or 6-membered heteroaryl, 6) a 4- to 10-membered non-aryl heterocycle, 7) a C₁₋₆ alkylcarbonyl group, 8) a C₃₋₁₀ alicyclic carbonyl group, 9) a C₆₋₁₀ arylcarbonyl group, 10) a 5- or 6-membered heteroarylcarbonyl group, 11) a C₁₋₆ alkylsulfonyl group, 12) a C₃₋₁₀ alicyclic sulfonyl group, 13) a C₆₋₁₀ arylsulfonyl group, 14) a 5- or 6-membered heteroarylsulfonyl group, or 15) —OR^(c1), (wherein each substituent from 2) to 14) is optionally substituted), wherein R^(a2) and R^(b1) together may form an optionally substituted 4- to 10-membered nitrogen-containing non-aryl heterocycle, R^(c1) is 1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₁₀ alicyclic group, 4) C₆₋₁₀ aryl, 5) 5- or 6-membered heteroaryl, or 6) a 4- to 10-membered non-aryl heterocycle, (wherein each substituent from 2) to 6) is optionally substituted), L¹ is a single bond, an oxygen atom, a sulfur atom, —SO—, —SO₂—, —NR^(d1)—, —NR^(d1)(═O)—, or —NR^(d1)SO₂—, L² is a single bond or an optionally substituted C₁₋₆ alkylene group, Z is 1) a hydrogen atom, 2) a hydroxyl group, 3) a cyano group, 4) a carboxyl group, 5) a C₃₋₁₀ alicyclic group, 6) C₆₋₁₀ aryl, 7) 5- or 6-membered heteroaryl, 8) a 4- to 10-membered non-aryl heterocycle, 9) a C₁₋₆ alkoxy group, 10) a C₃₋₁₀ alicyclic oxy group, 11) a C₆₋₁₀ aryloxy group, 12) a 5- or 6-membered heteroaryloxy group, 13) a 4- to 10-membered non-aryl heterocyclyl oxy group, 14) a C₁₋₆ alkylthio group, 15) a C₃₋₁₀ alicyclic thio group, 16) a C₆₋₁₀ arylthio group, 17) a 5- or 6-membered heteroarylthio group, 18) a 4- to 10-membered non-aryl heterocyclyl thio group, (wherein each substituent from 5) to 18) is optionally substituted), 19) —SO₂—NR^(e1)R^(f1), 20) —NR^(e1)—C(═O)OR^(f1), 21) —NR^(g1)—C(═O)NR^(e1)R^(f1), 22) —NR^(e1)—C(═S)R^(f1), 23) —NR^(e1)—C(═S)OR^(f1), 24) —NR^(g1)—C(═S)NR^(e1)R^(f1), 25) —NR^(g1)—CR^(e1)(═NR^(f1)), 26) —NR^(g1)—CR^(e1)(═N—OR^(e1)), 27) —NR^(h1)—C(═NR^(g1))NR^(e1)R^(f1), 28) —NR^(h1)—C(═N—OR^(g1))NR^(e1)R^(f1), 29) —NR^(i1)—C(═NR^(h1))NR^(g1)—NR^(e1)R^(f1), 30) —NR^(i1)—C(═N—OR^(h1))NR^(g1)—NR^(e1)R^(f1), 31) —NR^(e1)—SO₂—R^(f1), 32) —NR^(g1)—SO₂—NR^(e1)R^(f1), 33) —C(═O)OR^(e1), 34) —C(═S)OR^(e1), 35) —C(═S)NR^(e1)R^(f1), 36) —C(═S)NR^(e1)OR^(f1), 37) —C(═S)NR^(g1)—NR^(e1)R^(f1), 38) —C(═NR^(e1))R^(f1), 39) —C(═N—OR^(e1))R^(f1), 40) —C(═NR^(h1))NR^(g1)—NR^(e1)R^(f1), 41) —C(═N—OR^(h1))NR^(g1)—NR^(e1)R^(f1), 42) —NR^(e1)R^(f1), 43) —NR^(g1)—NR^(e1)R^(f1), 44) —NR^(e1)OR^(f1), 45) —NR^(e1)—C(═O)R^(f1), 46) —C(═O)NR^(e1)R^(f1), 47) —C(═O)NR^(e1)OR^(f1), 48) —C(═O)NR^(g1)—NR^(e1)R^(f1), 49) —C(═O)R^(e1), 50) —C(═NR^(g1))NR^(e1)R^(f1), or 51) —C(═N—OR^(h1))NR^(e1)R^(f1), one of R¹, R², and R³ is a group represented by formula (2):

wherein Y is an oxygen atom, a sulfur atom, or —NR^(j)—, ring A is an optionally substituted 4- to 20-membered non-aryl heterocycle, L³ is 1) an oxygen atom, 2) a sulfur atom, 3) —NR^(d2)—, 4) —NR^(d2)C(═O)—, 5) —NR^(d2)SO₂—, 6) a C₁₋₆ alkylene group, 7) a C₃₋₁₀ cycloalkylene group, 8) a 4- to 10-membered non-aryl heterocyclylene group, (wherein each substituent from 6) to 8) is optionally substituted), 9) —C(═O)—, 10) —S(═O)—, or 11) —S(═O)₂—, L⁴ is 1) a single bond, 2) a C₁₋₆ alkylene group, 3) a C₃₋₁₀ cycloalkylene group, 4) a C₆₋₁₀ arylene group, 5) a 5- or 6-membered heteroarylene group, 6) a 4- to 10-membered non-aryl heterocyclylene group, (wherein each substituent from 2) to 6) is optionally substituted), or 7) —C(═N—OR^(h1))—, R⁵ is 1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₁₀ alicyclic group, 4) a 4- to 10-membered non-aryl heterocycle, 5) C₆₋₁₀ aryl, 6) 5- to 10-membered heteroaryl, 7) a C₁₋₆ alkylthio group, (wherein each substituent from 2) to 7) is optionally substituted, and if two substituents further substituted with the substituent of 1), 2), or 3) are each substituted on adjacent atoms within a ring, the two substituents together may further form a condensed ring structure), 8) —NR^(e1)OH, 9) a carboxyl group (—C(═O)OH), 10) a carboxylic acid isostere (wherein the carboxylic acid isostere comprises an ester group-C(═O)OR^(20a), 11) a sulfo group (sulfonic acid group), 12) —SO₂R^(e1), 13) —SO₂—NR^(e1)R^(f1), 14) —S(═O)(═NR^(f1))R^(e1), 15) —NR^(e1)—C(═O)R^(f1), 16) —NR^(e1)—C(═O)OR^(f1), 17) —NR^(g1)—C(═O)NR^(e1)R^(f1), 18) —NR^(e1)—SO₂—R^(f1), 19) —NR^(g1)—SO₂—NR^(e1)R^(f1), 20) —N═S(═O)R^(e1)R^(f1), 21) —C(═O)NR⁵⁰R⁵¹, or 22) —NR^(e1)R^(f1) (wherein if R⁵ is the substituent of 22), -L³-L⁴-R⁵ is not —(CH₂)₁₋₄NR^(e1)R^(f1) (wherein R^(e1) and R^(f1) are a hydrogen atom, optionally substituted C₁₋₄ alkyl, an optionally substituted C₃₋₇ alicyclic group, an optionally substituted 4- to 10-membered non-aryl heterocyclic group, optionally substituted C₆₋₁₀ aryl, or optionally substituted 5- to 10-membered heteroaryl)), R^(20a) is 1) a C₁₋₆ alkyl group, 2) a C₃₋₁₀ alicyclic group, 3) C₆₋₁₀ aryl, 4) 5- or 6-membered heteroaryl, or 5) a 4- to 10-membered non-aryl heterocycle, (wherein each substituent from 1) to 5) is optionally substituted), R⁵⁰ represents 1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a hydroxyl group, 4) C₁₋₆ alkoxy group, 5) a C₃₋₆ cycloalkoxy group, 6) a C₃₋₆ alicyclic group, 7) a 4- to 6-membered non-aryl heterocycle, 8) C₆₋₁₀ aryl, 9) 5- to 10-membered heteroaryl, 10) 4- to 6-membered non-aryl heterocyclyl oxy, 11) C₆₋₁₀ aryloxy, 12) 5- to 10-membered heteroaryloxy, 13) a C₁₋₆ alkylsulfonyl group, 14) a C₃₋₆ cycloalkoxysulfonyl group, or 15) a 4- to 6-membered non-aryl heterocyclyl sulfonyl group, (wherein each substituent of 2) and 4) to 15) is optionally substituted), R⁵¹ represents 1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₆ alicyclic group, 4) a 4- to 6-membered non-aryl heterocycle, 5) C₆₋₁₀ aryl, or 6) 5- to 10-membered heteroaryl, (wherein each substituent from 2) to 6) is optionally substituted), or R⁵⁰ and R⁵¹ together may form optionally substituted 4- to 7-membered nitrogen-containing non-aryl heterocycle, the remaining two (without the structure of formula (2) among R¹, R², and R³) are the same or different, each independently a hydrogen atom, a halogen atom, an optionally substituted C₁₋₆ alkyl group, an optionally substituted C₁₋₆ alkoxy group, an optionally substituted C₁₋₆ alkylthio group, optionally substituted 5- or 6-membered heteroaryl, or —NR^(a3)R^(b2), R^(d1), R^(d2), R^(e1), R^(f1), R^(g1), R^(h1), R^(i1), and R^(j) are the same or different, each independently 1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₁₀ alicyclic group, 4) C₆₋₁₀ aryl, 5) 5- or 6-membered heteroaryl, or 6) a 4- to 10-membered non-aryl heterocycle, (wherein each substituent from 2) to 6) is optionally substituted), a combination of R^(e1) and R^(f1), when attached to the same nitrogen atom, together may form an optionally substituted 4- to 10-membered nitrogen-containing non-aryl heterocycle, R⁴ is 1) —C(═O)R⁸, 2) —SO₂-L⁶-R⁸, (wherein R⁸ in 1) and 2) is —NR^(a5)R^(b4), —NR^(a5)-L⁷-B(OR^(m1))₂, —OR^(m1), or an optionally substituted C₁₋₆ alkyl group, and L⁶ is a single bond or —NR^(a6)—), 3) —NR^(a4)R^(b3), 4) —B(OR^(m1))₂, 5) —PO(OR^(m1))(OR^(m2)), 6) optionally substituted 5-membered heteroaryl, 7) an optionally substituted 5-membered non-aryl heterocycle, or 8) a bioisostere of one of 1) to 7), (wherein the formulas of 2), 4), 5), and 6) include a carboxylic acid isostere, and 8) may include them in duplicates), R^(a3), R^(a4), R^(a5), R^(a6), R^(b2), R^(b3), and R^(b4) are the same or different, each independently having the same definition as R^(a1), R^(a2), and R^(b1), wherein a combination of R^(a3) and R^(b2), R^(a4) and R^(b3), or R^(a5) and R^(b4), when attached to the same nitrogen atom, together may form an optionally substituted 4- to 10-membered nitrogen-containing non-aryl heterocycle, R^(m1) is 1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₁₀ alicyclic group, 4) C₆₋₁₀ aryl, 5) 5- or 6-membered heteroaryl, or 6) a 4- to 10-membered non-aryl heterocycle, (wherein each substituent from 2) to 6) is optionally substituted), wherein if R^(m1) is attached to a boron atom via an oxygen atom, two R^(m1), as C₂₋₄ alkylene, together with the boron atom and two oxygen atoms, may form a 5- to 7-membered non-aryl heterocycle (wherein an alkylene moiety is optionally substituted in the non-aryl heterocycle), R^(m2) is a hydrogen atom, an optionally substituted C₁₋₆ alkyl group, or an optionally substituted C₃₋₁₀ alicyclic group, L⁷ is an optionally substituted C₁₋₃ alkylene group, R⁶¹, R⁶², and R⁶³ are each independently a hydrogen atom, halogen, or an optionally substituted C₁₋₆ alkyl group, and R⁶⁴ is a hydrogen atom, halogen, an optionally substituted C₁₋₆ alkyl group, or -L¹-L²-Z.
 4. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 3, wherein L³ is 1) a C₁₋₆ alkylene group, 2) a C₃₋₁₀ cycloalkylene group, or 3) a 4- to 10-membered non-aryl heterocyclylene group, (wherein each substituent from 1) to 3) is optionally substituted), and L⁴ is a single bond or an optionally substituted C₁₋₅ alkylene group.
 5. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 4, wherein L³ is an optionally substituted C₁₋₄ alkylene group, and L⁴ is a single bond or an optionally substituted C₁₋₃ alkylene group.
 6. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 5, wherein L³ is —(CR³⁰R³¹)_(n1)—, R³⁰ and R³¹ are each independently, or if there are multiple instances of each of them, all of them independently represent 1) a hydrogen atom, 2) —NR^(a7)R^(a8), 3) a C₁₋₄ alkyl group, 4) C₆₋₁₀ aryl, 5) 5- to 10-membered heteroaryl, 6) a C₃₋₆ alicyclic group, 7) a 4- to 10-membered non-aryl heterocycle, (wherein each substituent from 3) to 7) is optionally substituted), or 8) —OR^(c2), or R³⁰ and R³¹, together with the carbon atom to which they are attached, form a C₃₋₆ alicyclic group or a 4- to 6-membered non-aryl heterocycle, R^(a7) and R^(a8) are the same or different, each independently 1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₁₀ alicyclic group, 4) C₆₋₁₀ aryl, 5) 5- or 6-membered heteroaryl, 6) a 4- to 10-membered non-aryl heterocycle, 7) a C₁₋₆ alkylcarbonyl group, 8) a C₃₋₁₀ alicyclic carbonyl group, 9) a C₆₋₁₀ arylcarbonyl group, 10) a 5- or 6-membered heteroarylcarbonyl group, 11) a C₁₋₆ alkylsulfonyl group, 12) a C₃₋₁₀ alicyclic sulfonyl group, 13) a C₆₋₁₀ arylsulfonyl group, 14) a 5- or 6-membered heteroarylsulfonyl group, or 15) —OR^(c3), (wherein each substituent from 2) to 14) is optionally substituted), wherein R^(a7) and R^(a8) together may form an optionally substituted 4- to 10-membered nitrogen-containing non-aryl heterocycle, R^(c2) and R^(c3) are each independently 1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₁₀ alicyclic group, 4) C₆₋₁₀ aryl, 5) 5- or 6-membered heteroaryl, or 6) a 4- to 10-membered non-aryl heterocycle, (wherein each substituent from 2) to 6) is optionally substituted), n1 is an integer 1, 2, 3, or 4, L⁴ is —(CR⁴⁰R⁴¹)_(n2)—, R⁴⁰ and R⁴¹ each independently, or if there are multiple instances of each of them, all of them independently represent 1) a hydrogen atom, 2) —NR^(a9)R^(a10), 3) a C₁₋₄ alkyl group, 4) C₆₋₁₀ aryl, 5) 5- to 10-membered heteroaryl, 6) a C₃₋₆ alicyclic group, 7) a 4- to 10-membered non-aryl heterocycle, (wherein each substituent from 3) to 7) is optionally substituted), or 8) —OR^(c4), or R⁴⁰ and R⁴¹, together with the carbon atom to which they are attached, form a C₃₋₆ alicyclic group or a 4- to 6-membered non-aryl heterocycle, R^(a9) and R^(a10) are the same or different, each independently 1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₁₀ alicyclic group, 4) C₆₋₁₀ aryl, 5) 5- or 6-membered heteroaryl, 6) a 4- to 10-membered non-aryl heterocycle, 7) a C₁₋₆ alkylcarbonyl group, 8) a C₃₋₁₀ alicyclic carbonyl group, 9) a C₆₋₁₀ arylcarbonyl group, 10) a 5- or 6-membered heteroarylcarbonyl group, 11) a C₁₋₆ alkylsulfonyl group, 12) a C₃₋₁₀ alicyclic sulfonyl group, 13) a C₆₋₁₀ arylsulfonyl group, 14) a 5- or 6-membered heteroarylsulfonyl group, (wherein each substituent from 2) to 14) is optionally substituted), or 15) —OR^(c5), wherein R^(a9) and R^(a10) together may form an optionally substituted 4- to 10-membered nitrogen-containing non-aryl heterocycle, R^(c4) and R^(c5) are each independently defined the same as R^(c2) and R^(c3), and n2 is an integer 0 (i.e., when L⁴ is a single bond), 1, 2, or
 3. 7. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 6, wherein -L³-L⁴- is an optionally substituted C₁₋₂ alkylene group.
 8. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 7, wherein -L³-L⁴- is a C₁₋₂ alkylene group optionally substituted with a C₁₋₃ alkyl group, an amino group, or a hydroxymethyl group, or a plurality of the same or different groups thereamong (wherein two C₁₋₃ alkyl groups, when attached to the same carbon atom, together with the carbon atom to which they are attached, may form a C₃₋₆ alicyclic group).
 9. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 8, wherein R⁵ is 1) a C₃₋₁₀ alicyclic group, 2) C₆₋₁₀ aryl, 3) 5- to 10-membered heteroaryl, 4) a C₁₋₆ alkylthio group, (wherein each substituent from 1) to 4) is optionally substituted, and if two substituents further substituted with the substituent of 2) or 3) are each substituted on adjacent atoms within a ring, the two substituents together may further form a condensed ring structure), 5) —NR^(e1)OH, 6) —C(═O)NR⁵⁰R⁵¹, 7) —SO₂—NR^(e1)R^(f1), 8) —NR^(e1)—SO₂—R^(f1), 9) —C(═O)OR²⁰, or 10) —NR^(e1)R^(f1) (wherein if R⁵ is the substituent of 10), L³ and/or L⁴ is a C₁₋₆ alkylene group that is necessarily substituted with one or more groups other than a hydrogen atom (wherein L³ or L⁴, together with said substituent, may form a C₃₋₁₀ alicyclic group or a 4- to 10-membered non-aryl heterocycle)), and R²⁰ is 1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₁₀ alicyclic group, 4) C₆₋₁₀ aryl, 5) 5- or 6-membered heteroaryl, or 6) a 4- to 10-membered non-aryl heterocycle, (wherein each substituent from 2) to 6) is optionally substituted).
 10. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 9, wherein R⁵ is 1) C₆₋₁₀ aryl, 2) 5- to 10-membered heteroaryl, 3) —C(═O)NR⁵⁰R⁵¹, 4) —C(═O)OR²⁰, or 5) —NR^(e1)R^(f1) (wherein if R⁵ is the substituent of 5), L³ and/or L⁴ is a C₁₋₆ alkylene group that is necessarily substituted with one or more groups other than a hydrogen atom, and together with said substituent forms at least one C₃₋₁₀ alicyclic group or 4- to 10-membered non-aryl heterocycle), (wherein each substituent from 1) to 2) is optionally substituted, and any two groups thereof, when each is attached to adjacent atoms within a ring, together may further form a condensed ring structure).
 11. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 10, wherein Z-L²-L¹ is an optionally substituted C₁₋₆ alkylthio group.
 12. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 11, wherein R⁶¹, R⁶², R⁶³, and R⁶⁴ are each independently a hydrogen atom, a fluorine atom, or a C₁₋₃ alkyl group optionally substituted with a fluorine atom.
 13. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 12, wherein R⁶¹, R⁶², R⁶³, and R⁶⁴ are each independently a hydrogen atom or a fluorine atom.
 14. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 13, wherein G is an oxygen atom.
 15. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 14, wherein X is a hydroxyl group or an optionally substituted C₁₋₆ alkoxy group.
 16. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 15, wherein X is a hydroxyl group.
 17. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 16, wherein the compounds of formulas (1a) and (1b) are represented by formulas (3a) and (3b), respectively:

wherein X, R¹, R², and R³ are defined the same as any one of claims 1 to 16, and R⁴ is selected from the group consisting of 1) —C(═O)OR^(m1) (wherein R^(m1) is a hydrogen atom, a C₁₋₆ alkyl group, a C₃₋₁₀ alicyclic group, C₆-10 aryl, 5- or 6-membered heteroaryl, or a 4- to 10-membered non-aryl heterocycle, wherein the C₁₋₆ alkyl group, the C₃₋₁₀ alicyclic group, the C₆₋₁₀ aryl, the 5- or 6-membered heteroaryl, and the 4- to 10-membered non-aryl heterocycle are each optionally substituted), and 2) a bioisostere of 1).
 18. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 17, wherein R⁴ is 1) —C(═O)OH (i.e., a carboxyl group), or 2) a carboxylic acid isostere.
 19. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 18, wherein the compounds of formulas (1a) and (1b) or the compounds of formulas (3a) and (3b) are represented by formulas (4a) and (4b), respectively:

wherein X, R⁴, Y, ring A, L³, L⁴, and R⁵ are defined the same as any one of claims 1 to 18, and R¹ and R² are the same or different, each independently a hydrogen atom, a halogen atom, a C₁₋₆ alkyl group, a C₁₋₆ alkoxy group, or a C₁₋₆ alkylthio group (wherein the C₁₋₆ alkyl group, C₁₋₆ alkoxy group, and C₁₋₆ alkylthio group are optionally substituted).
 20. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 19, wherein ring A is an optionally substituted 4- to 10-membered non-aryl heterocycle.
 21. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 20, wherein ring A is an optionally substituted 4- to 7-membered non-aryl heterocycle.
 22. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 21, wherein Y is an oxygen atom or a sulfur atom.
 23. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 22, wherein Y is an oxygen atom.
 24. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 23, wherein the compounds of formulas (1a) and (1b), the compounds of formulas (3a) and (3b), or the compounds of formulas (4a) and (4b) are represented by formulas (5a) and (5b), respectively:

wherein R¹, R², Y, L³, L⁴, and R⁵ are defined the same as any one of claims 1 to 23, and ring A is an optionally substituted 4- to 6-membered nitrogen-containing non-aryl heterocycle.
 25. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 3 and 11 to 24, wherein L³ is —C(═O)— or —S(═O)₂—.
 26. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 3 and 11 to 25, wherein L³ is —C(═O)—.
 27. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 3 and 11 to 26, wherein L⁴ is a single bond, —C(═N—OR^(h1))—, or an optionally substituted C₁₋₆ alkylene group, wherein R^(h1) is an optionally substituted C₁₋₆ alkyl group.
 28. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 27, wherein R¹ and R² are the same or different, each independently selected from the group consisting of 1) a hydrogen atom, 2) a halogen atom, 3) a C₁₋₆ alkyl group, 4) a C₁₋₆ alkoxy group, and 5) a C₁₋₆ alkylthio group, (wherein each substituent from 3) to 5) is optionally substituted).
 29. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 28, wherein R¹ and R² are the same or different, each independently selected from the group consisting of 1) a hydrogen atom, 2) a halogen atom, 3) a C₁₋₆ alkyl group, 4) a C₁₋₆ alkoxy group, and 5) a C₁₋₆ alkylthio group, (wherein each substituent from 3) to 5) is optionally substituted with a halogen atom).
 30. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 29, wherein R¹ and R² are the same or different, each independently selected from the group consisting of 1) a hydrogen atom, 2) a halogen atom, and 3) a C₁₋₆ alkyl group optionally substituted with a halogen atom.
 31. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 30, wherein R¹ and R² are the same or different, each independently selected from the group consisting of 1) a hydrogen atom, 2) a fluorine atom, and 3) a C₁₋₃ alkyl group optionally substituted with a fluorine atom.
 32. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 31, wherein R¹ and R² are both hydrogen atoms.
 33. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 32, wherein the compounds of formulas (1a) and (1b), the compounds of formulas (3a) and (3b), the compounds of formulas (4a) and (4b), or the compounds of formulas (5a) and (5b) are represented by formulas (6a) and (6b), respectively:

wherein L³, L⁴, and R⁵ are defined the same as any one of claims 1 to 32, m is an integer 1, 2, or 3, n is an integer 1, 2, or 3, and m+n is 2, 3, or
 4. 34. The compound or the pharmaceutically acceptable salt thereof according to claim 33, wherein the compounds of formulas (6a) and (6b) are enantiomers represented by formulas (7a) and (7b):

formulas (8a) and (8b):

 respectively, wherein L³, L⁴, and R³ are defined the same as any one of claims 1 to 33, and m and n are defined the same as claim
 33. 35. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 34, wherein m is 1 or 2, n is 1 or 2, and m+n is 2 or
 3. 36. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 35, wherein m is 1, and n is
 1. 37. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 6, 9 to 24, and 28 to 36, wherein L³ is —(CR³⁰R³¹)_(n1)— or 4- to 10-membered non-aryl heterocyclylene, R³⁰ and R³¹ each independently, or if there are multiple instances of each of them, all of them independently represent 1) a hydrogen atom, 2) an optionally substituted C₁₋₄ alkyl group, or 3) optionally substituted C₆₋₁₀ aryl, n1 is 1, 2, or 3, L⁴ is a single bond or —(CR⁴⁰R⁴¹)_(n2)—, R⁴⁰ and R⁴¹ each independently, or if there are multiple instances of each of them, all of them independently represent 1) a hydrogen atom, 2) —NR^(a9)R^(a10), 3) an optionally substituted C₁₋₄ alkyl group, or 4) —OR^(c4) or R⁴⁰ and R⁴¹, together with the carbon atom to which they are attached, form a C₃₋₆ alicyclic group or a 4- to 6-membered non-aryl heterocycle, R^(a9), R^(a10), and R^(c4) are the same or different, each independently 1) a hydrogen atom, 2) an optionally substituted C₁₋₆ alkyl group, or 3) an optionally substituted C₃₋₁₀ alicyclic group, wherein R^(a9) and R^(a10) together may form an optionally substituted 4- to 10-membered nitrogen-containing non-aryl heterocycle, and n2 is 0, 1, or
 2. 38. The compound or the pharmaceutically acceptable salt thereof according to claim 37, wherein n1 is 1 or 2, and n2 is 0 or
 1. 39. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 6, 9 to 24, and 28 to 38, wherein L³ is —CR³⁰R³¹— or 4- to 10-membered non-aryl heterocyclylene, R³⁰ and R³¹ each independently represent, 1) a hydrogen atom, 2) a C₁₋₄ alkyl group (wherein the group is optionally substituted with halogen, —NR^(a11)R^(a12), or —OR^(c6)), or 3) C₆ aryl (wherein the group is optionally substituted with halogen, —NR^(a13)R^(a14), —OR^(c7), or a C₁₋₃ alkyl group (wherein the group is optionally substituted with halogen, —NR^(a15)R^(a16), or —OR^(c8))), L⁴ is a single bond or —(CR⁴⁰R⁴¹)_(n2)—, R⁴⁰ and R⁴¹ each independently represent 1) a hydrogen atom, 2) —NR^(a9)R^(a10), 3) a C₁₋₄ alkyl group (wherein the group is optionally substituted with halogen, —NR^(a17)R^(a18), or —OR^(c9)), or 4) —OR^(c4), or R⁴⁰ and R⁴¹, together with the carbon atom to which they are attached, form a C₃₋₆ alicyclic group, R^(a9), R^(a10), R^(a11), R^(a12), R^(a13), R^(a14), R^(a15), R^(a16), R^(a17), R^(a18), R^(c4), R^(c6), R^(c7), R^(c8), and R^(c9) are the same or different, each independently representing 1) a hydrogen atom, or 2) a C₁₋₄ alkyl group (wherein the group is optionally substituted with halogen, —NR^(a19)R^(a20), or —OR^(c10)), R^(a19), R^(a20), and R^(c10) are the same or different, each independently representing 1) a hydrogen atom, or 2) a C₁₋₄ alkyl group (wherein the group is optionally substituted with halogen), wherein each combination of R^(a9) and R^(a10), R^(a11) and R^(a12), R^(a13) and R^(a14), R^(a15) and R^(a16), R^(a17) and R^(a18), or R^(a19) and R^(a20) together may form an optionally substituted 4- to 7-membered nitrogen-containing non-aryl heterocycle, and n2 is 0 or
 1. 40. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 6, 9 to 24, and 28 to 39, wherein L³ is —CH₂—, —CH(CH₂NH₂)—, or —CH(CH₂OH)—, and L⁴ is a single bond, —CH₂—, —CH(NH₂)—, —CMe(NH₂)—, —CEt(NH₂)—, —C(iso-Pr)(NH₂)—, —CH(CH₂NH₂)—, —CH(OH)—, —CH(CH₂OH)—, —C(CH₂OH)₂—, or


41. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 6, 9 to 24, and 28 to 39, wherein L³ is 4- to 10-membered non-aryl heterocyclylene.
 42. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 6, 9 to 24, 28 to 39, and 41, wherein L³ is 5-membered non-aryl heterocyclylene.
 43. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 6, 9 to 24, 28 to 39, and 41 to 42, wherein L³ is


44. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 6, 9 to 24, 28 to 39, and 41 to 43, wherein L⁴ is a single bond.
 45. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 24 and 28 to 40, wherein R⁵ is 1) C₆₋₁₀ aryl, or 2) 5- to 10-membered heteroaryl, (wherein each substituent from 1) to 2) is optionally substituted, and if two substituents further substituted with the substituent of 1) or 2) are each substituted on adjacent atoms within a ring, the two substituents together may further form a condensed ring structure).
 46. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 24 and 28 to 45, wherein R⁵ is C₆ aryl (i.e., phenyl) or 5-membered, 6-membered, 9-membered, or 10-membered heteroaryl, each group of R⁵ is optionally substituted with each of R^(6a) or R^(6b) at all chemically substitutable positions on a carbon atom or a nitrogen atom within a ring thereof, wherein R^(6a), which are substituents on the carbon atom, if there are multiple instances on the same ring, are all independently selected from the group consisting of 1) a hydrogen atom, 2) a hydroxyl group, 3) a cyano group, 4) halogen, 5) a C₁₋₄ alkyl group, 6) a C₃₋₁₀ alicyclic group, 7) a C₁₋₄ alkoxy group, 8) a C₃₋₁₀ alicyclic oxy group, 9) a C₆₋₁₀ aryloxy group, 10) a 5- or 6-membered heteroaryloxy group, 11) a 4- to 10-membered non-aryl heterocyclyl oxy group, (wherein each substituent from 5) and 11) is optionally substituted), 12) —SO₂—NR^(e2)R^(f2), 13) —NR^(g2)—CR^(e2)(═NR^(f2)), 14) —NR^(g2)—CR^(e2)(═N—OR^(f2)), 15) —NR^(h2)—C(═NR^(g2))NR^(e2)R^(f2), 16) —NR^(h2)—C(═N—OR^(g2))NR^(e2)R^(f2), 17) —NR^(i2)—C(═NR^(h2))NR^(g2)—NR^(e2)R^(f2), 18) —NR^(i2)—C(═N—OR^(h2))NR^(g2)—NR^(e2)R^(f2), 19) —C(═NR^(e2))R^(f2), 20) —C(═N—OR^(e2))R^(f2), 21) —C(═NR^(h2))—NR^(e2)R^(f2), 22) —C(═NR^(h2))NR^(g2)—NR^(e2)R^(f2), 23) —C(═N—OR^(h2))NR^(g2)—NR^(e2)R^(f2), 24) —NR^(e2)R^(f2), 25) —NR^(g2)—NR^(e2)R^(f2), 26) —NR^(e2)OR^(f2), 27) —NR^(e2)—C(═O)R^(f2), 28) —C(═O)NR^(e2)R^(f2), 29) —C(═O)NR^(e2)OR^(f2), 30) —C(═O)NR^(g2)—NR^(e2)R^(f2), 31) —C(═O)R^(e2), 32) —C(═O)OR^(e2), and 33) —C(═N—OR^(h2))NR^(e2)R^(f2), R^(6b), which are substituents on the nitrogen atom, if there are multiple instances on the same ring, are all independently selected from the group consisting of 1) a hydrogen atom, 2) a hydroxyl group, 3) a C₁₋₄ alkyl group (wherein the alkyl group is optionally substituted), 4) a C₃₋₁₀ alicyclic group (wherein the alicyclic group is optionally substituted), 5) —C(═NR^(e2))R^(f2), 6) —C(═N—OR^(e2))R^(f2), 7) —SO₂—NR^(e2)R^(f2), 8) —C(═NR^(h2))—NR^(e2)R^(f2), 9) —C(═NR^(h2))NR^(g2)—NR^(e2)R^(f2), 10) —C(═N—OR^(h2))NR^(g2)—NR^(e2)R^(f2), 11) —C(═O)NR^(e2)R^(f2), 12) —C(═O)NR^(e2)OR^(f2), 13) —C(═O)NR^(g2)—NR^(e2)R^(f2), 14) —C(═O)R^(e2), and 15) —C(═N—OR^(h2))NR^(e2)R^(f2), or if a combination of two R^(6a) or R^(6a) and R^(6b) are each substituted on adjacent atoms within a ring, the two substituents together may form an optionally substituted 5- to 6-membered heteroaryl ring or an optionally substituted 5- to 7-membered non-aryl heterocycle, which further fuses to an attachment moiety between the adjacent atoms within the ring, R^(e2), R^(f2), R^(g2), R^(h2), and R^(i2) are the same or different, each independently 1) a hydrogen atom, 2) a C₁₋₆ alkyl group, 3) a C₃₋₁₀ alicyclic group, 4) C₆₋₁₀ aryl, 5) 5- or 6-membered heteroaryl, or 6) a 4- to 10-membered non-aryl heterocycle, (wherein each substituent from 2) to 6) is optionally substituted), and a combination of R^(e2) and R^(f2), when attached to the same nitrogen atom, together may form an optionally substituted 4- to 10-membered nitrogen-containing non-aryl heterocycle.
 47. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 24 and 28 to 46, wherein R⁵ is C₆ aryl or 5-membered, 6-membered, 9-membered, or 10-membered heteroaryl selected from the group consisting of

d is the number of chemically substitutable positions on a ring of each group by R^(6a), and each R^(6a) and each R^(6b) are defined the same as claim
 46. 48. The compound or the pharmaceutically acceptable salt thereof according to claim 46 or 47, wherein R⁶, if there are multiple instances on the same ring, are all independently selected from the group consisting of 1) a hydrogen atom, 2) a hydroxyl group, 3) halogen, 4) a C₁₋₄ alkyl group, (wherein the alkyl group is optionally substituted with NR^(e2)R^(f2), C(═O)OR^(f2), —C(═O)NR^(e2)R^(f2), —C(═O)NR^(e2)(OR^(f2)), or a hydroxyl group), 5) a C₁₋₄ alkoxy group, 6) —NR^(e2)R^(f2), 7) —C(═O)NR^(e2)R^(f2), and 8) —C(═O)OR^(e2), and each of R^(6b), if there are multiple instances on the same ring, are all independently selected from the group consisting of 1) a hydrogen atom, 2) a hydroxyl group, and 3) a C₁₋₄ alkyl group, (wherein the alkyl group is optionally substituted with NR^(e2)R^(f2), C(═O)OR^(f2), —C(═O)NR^(e2)R^(f2), —C(═O)NR^(e2)(OR^(f2)), or a hydroxyl group).
 49. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 24 and 28 to 48, wherein R^(e2) and R^(f2) are the same or different, each independently a hydrogen atom, an optionally substituted C₁₋₆ alkyl group, or an optionally substituted C₃₋₁₀ alicyclic group.
 50. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 24 and 28 to 49, wherein R^(e2) and R^(f2) are the same or different, each independently a hydrogen atom or an optionally substituted C₁₋₆ alkyl group.
 51. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 24 and 28 to 50, wherein R^(e2) and R^(f2) are hydrogen atoms.
 52. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 46 to 51, wherein R^(6a) is —NR^(e2)R^(f2), and one of R^(e2) and R^(f2) is a hydrogen atom and the other is a C₁₋₄ alkyl group (wherein the alkyl group is optionally substituted with an amino group or a hydroxyl group).
 53. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 24 and 28 to 44, wherein R⁵ is —C(═O)NR⁵⁰R⁵¹.
 54. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 24, 28 to 40, and 53, wherein R⁵⁰ represents 1) a hydrogen atom, 2) an optionally substituted C₁₋₄ alkyl group, 3) a hydroxyl group, 4) an optionally substituted C₁₋₄ alkoxy group, or 5) an optionally substituted C₁₋₆ alkylsulfonyl group, R⁵¹ represents 1) a hydrogen atom, or 2) an optionally substituted C₁₋₄ alkyl group, or R⁵⁰ and R⁵¹ together may form a 4- to 6-membered nitrogen-containing non-aryl heterocycle.
 55. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 24, 28 to 40, and 53 to 54, wherein R⁵⁰ represents 1) a hydrogen atom, 2) a C₁₋₄ alkyl group (wherein the group is optionally substituted with halogen, a C₃₋₆ alicyclic group, —NR^(a21)R^(a22), or —OR^(c11)), 3) a hydroxyl group, 4) a C₁₋₄ alkoxy group (wherein the group is optionally substituted with halogen, a C₃₋₆ alicyclic group, —NR^(a23)R^(a24), or —OR^(c2), or 5) a C₁₋₄ alkylsulfonyl group (wherein the group is optionally substituted with halogen, a C₃₋₆ alicyclic group, —NR^(a21)R^(a22), or —OR^(c11)), R^(a21), R^(a22), R^(a23), R²⁴, R^(c11), and R^(c12) are the same or different, each independently representing 1) a hydrogen atom, or 2) a C₁₋₄ alkyl group (wherein the group is optionally substituted with halogen), wherein each combination of R^(a21) and R^(a22) or R^(a23) and R^(a24) together may form an optionally substituted 4- to 7-membered nitrogen-containing non-aryl heterocycle, and R⁵¹ is a hydrogen atom or C₁₋₄ alkyl (wherein the group is optionally substituted with halogen).
 56. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 24, 28 to 40, and 53 to 55, wherein R⁵⁰ represents 1) a hydrogen atom, 2) a C₁₋₄ alkyl group (wherein the group is optionally substituted with a cyclopropyl group, —NH₂, —NHMe, —C(═O)NH₂, —C(═O)NHMe, —C(═O)NMe₂, or a -hydroxyl group), 3) a hydroxyl group, 4) a C₁₋₄ alkoxy group (wherein the group is optionally substituted with a cyclopropyl group, —NH₂, —NHMe, or a -hydroxyl group), or 5) a C₁₋₄ alkylsulfonyl group, and R⁵¹ is a hydrogen atom.
 57. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 24 and 28 to 40, wherein R⁵ is —C(═O)OR²⁰.
 58. The compound or the pharmaceutically acceptable salt thereof according to claim 57, wherein R²⁰ is 1) a hydrogen atom, or 2) an optionally substituted C₁₋₄ alkyl group.
 59. The compound or the pharmaceutically acceptable salt thereof according to claim 56 or 58, wherein L³ is —CH₂—, and L⁴ is a single bond, —CH(NH₂)—, or —CMe(NH₂)—.
 60. The compound or the pharmaceutically acceptable salt thereof according to claim 59, wherein L⁴ is


61. The compound or the pharmaceutically acceptable salt thereof according to claim 59 or 60, wherein L⁴ is


62. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 57 to 61, wherein R²⁰ is a hydrogen atom.
 63. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 24 and 28 to 40, wherein R⁵ is —NR^(e1)R^(f1), L³ is —CH₂—, L⁴ is —CR⁴⁰R⁴¹—, and R⁴⁰ and R⁴¹ are each independently a C₁₋₄ alkyl group substituted with a hydroxyl group, or together with the carbon atom to which they are attached, form a C₃₋₆ alicyclic group.
 64. The compound or the pharmaceutically acceptable salt thereof according to claim 63, wherein R^(e1) and R^(f1) are the same or different, each independently 1) a hydrogen atom, or 2) an optionally substituted C₁₋₃ alkyl group, and L⁴ is


65. The compound or the pharmaceutically acceptable salt thereof according to claim 63, wherein R^(e1) and R^(f1) are the same or different, each independently 1) a hydrogen atom, or 2) an optionally substituted C₁₋₃ alkyl group, and L⁴ is a C₁₋₄ alkylene group substituted with a hydroxyl group.
 66. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 3 and 11 to 36, wherein L⁴ is a single bond, or a C₁₋₆ alkylene group optionally substituted with —NR²¹R²² or ═NOR²³, wherein R²¹, R²², and R²³ are each independently a hydrogen atom, an optionally substituted C₁₋₆ alkyl group, or an optionally substituted 4- to 10-membered non-aryl heterocyclyl carbonyl group.
 67. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 3, 11 to 36, and 66, wherein L⁴ is a single bond, —CH₂—, —CH(NH₂)—, —CMe(NH₂)—, —CH(NHMe)-, —CD(NH₂)— (wherein D represents a heavy hydrogen atom), —CH₂CH₂—, or —CH(NH₂)—CH₂—, wherein if an amino group is present in L⁴, carbon that attaches to the amino group attaches to L³.
 68. The compound or the pharmaceutically acceptable salt thereof according to claim 67, wherein L³ is —C(═O)—, and L⁴ is a single bond, —CH₂—, —CH(NH₂)—, —CMe(NH₂)—, or —CH(NH₂)—CH₂—.
 69. The compound or the pharmaceutically acceptable salt thereof according to claim 68, wherein L⁴ is one of the following isomeric structures:


70. The compound or the pharmaceutically acceptable salt thereof according to claim 68 or 69, wherein L⁴ is


71. The compound or the pharmaceutically acceptable salt thereof according to claim 68 or 69, wherein L⁴ is


72. The compound or the pharmaceutically acceptable salt thereof according to claim 68 or 69, wherein L⁴ is


73. The compound or the pharmaceutically acceptable salt thereof according to claim 68 or 69, wherein L⁴ is


74. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 3, 11 to 36, and 66 to 73, wherein R⁵ is a hydrogen atom, an optionally substituted C₁₋₆ alkyl group, an optionally substituted C₃₋₁₀ alicyclic group, an optionally substituted 4- to 10-membered non-aryl heterocycle, optionally substituted C₆₋₁₀ aryl, optionally substituted 5- or 6-membered heteroaryl, an optionally substituted C₁₋₆ alkylthio group, or —NR^(e1)OH, wherein R^(e1) is a hydrogen atom or an optionally substituted C₁₋₆ alkyl group.
 75. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 3, 11 to 36, and 66 to 74, wherein R⁵ is optionally substituted 5- or 6-membered heteroaryl or optionally substituted C₆₋₁₀ aryl.
 76. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 3, 11 to 36, and 66 to 75, wherein R⁵ is optionally substituted 5- or 6-membered heteroaryl.
 77. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 3, 11 to 36, and 66 to 76, wherein R⁵ is an optionally substituted C₄₋₁₀ alicyclic group or an optionally substituted 4- to 10-membered non-aryl heterocycle.
 78. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 3, 11 to 36, and 66 to 74, wherein L⁴ is a single bond and R⁵ is —NR^(e1)OH, wherein R^(e1) is a hydrogen atom or an optionally substituted C₁₋₆ alkyl group.
 79. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 3 and 11 to 36, wherein L⁴ is 1) —(CH₂)_(p)—CR¹⁰(NHR¹¹)—, 2) —(CH₂)_(q)—CR¹²R¹³—, or 3) —(CH₂)_(p)—CR¹⁰(NHR¹¹)—(CH₂)_(q)—CR¹²R¹³— (wherein p and q are independently 0 or 1), R¹⁰ is 1) a hydrogen atom, 2) a carboxyl group, or 3) —C(═O)NR^(10a)R^(10b), R¹¹ is 1) a hydrogen atom, 2) —C(═O)R a, or 3) an optionally substituted 5- or 6-membered non-aryl heterocyclyl carbonyl group, wherein if R¹⁰ is —C(═O)NR^(10a)R^(10b), R^(10b) and R¹¹ together may form —CH₂CH₂—, R² is 1) a hydrogen atom, or 2) an optionally substituted C₁₋₄ alkyl group, R¹³ is 1) a hydrogen atom, 2) a hydroxyl group, 3) an optionally substituted C₁₋₄ alkyl group, 4) a sulfanyl group, 5) a carboxyl group, 6) an optionally substituted C₁₋₄ alkylthio group, 7) —NR^(13a)R^(13b), 8) —NR^(13a)—C(═O)R^(13b), 9) an optionally substituted 5- or 6-membered non-aryl heterocyclyl carbonylamino group, 10) —NR^(13a)—C(═O)NR^(13b)R^(13c), 11) —C(═O)NR^(13a)R^(13b), 12) —C(═O)NR^(13a)OR^(13b), 13) —S(═O)₂—R^(13a), 14) —S(═O)₂—NR^(13a)R^(13b), 15) —C(═O)NR^(13a)—S(═O)₂—R^(13b), or 16) —C(═O)NR^(13a)—S(═O)₂—NR^(13b)R^(13c), and R^(10a), R^(10b), R^(11a), R^(13a), R^(13b), and R^(13c) are each independently a hydrogen atom or an optionally substituted C₁₋₄ alkyl group.
 80. The compound or the pharmaceutically acceptable salt thereof according to claim 79, wherein R⁵ is a hydrogen atom or an optionally substituted C₁₋₄ alkyl group.
 81. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 3, 11 to 36, and 66 to 76, wherein R⁵ is selected from the group consisting of

subscript d is the number of substitutable positions on a ring of R⁵, each R^(6a) is independently selected from the group consisting of 1) a hydrogen atom, 2) a hydroxyl group, 3) a cyano group, 4) a nitro group, 5) halogen, 6) a C₁₋₄ alkyl group, 7) a C₃₋₁₀ alicyclic group, 8) a C₁₋₄ alkoxy group, 9) a C₃₋₁₀ alicyclic oxy group, 10) a C₆₋₁₀ aryloxy group, 11) a 5- or 6-membered heteroaryloxy group, 12) a 4- to 10-membered non-aryl heterocyclyl oxy group, (wherein each substituent from 6) to 12) is optionally substituted), 13) —SO₂—NR^(e2)R^(f2), 14) —NR^(g2)—CR^(e2)(═NR^(f2)), 15) —NR^(g2)—CR^(e2)(═N—OR^(f2)), 16) —NR^(h2)—C(═NR^(g2))NR^(e2)R^(f2), 17) —NR^(h2)—C(═N—OR^(g2))NR^(e2)R^(f2), 18) —NR^(i2)—C(═NR^(h2))NR^(g2)—NR^(e2)R^(f2), 19) —NR^(i2)—C(═N—OR^(h2))NR^(g2)—NR^(e2)R^(f2), 20) —C(═NR^(e2))R^(f2), 21) —C(═N—OR^(e2))R^(f2), 22) —C(═NR^(h2))—NR^(e2)R^(f2), 23) —C(═NR^(h2))NR^(g2)—NR^(e2)R^(f2), 24) —C(═N—OR^(h2))NR^(g2)—NR^(e2)R^(f2), 25) —NR^(e2)R^(f2), 26) —NR^(g2)—NR^(e2)R^(f2), 27) —NR^(e2)OR^(f2), 28) —NR^(e2)—C(═O)R^(f2), 29) —C(═O)NR^(e2)R^(f2), 30) —C(═O)NR^(e2)OR^(f2), 31) —C(═O)NR^(g2)—NR^(e2)R^(f2), 32) —C(═O)R^(e2), 33) —C(═O)OR^(e2), and 34) —C(═N—OR^(h2))NR^(e2)R^(f2), and each R^(6b) is independently selected from the group consisting of 1) a hydrogen atom, 2) a hydroxyl group, 3) a C₁₋₄ alkyl group (wherein the alkyl group is optionally substituted), 4) a C₃₋₁₀ alicyclic group (wherein the alicyclic group is optionally substituted), 5) —C(═NR^(e2))R^(f2), 6) —C(═N—OR^(e2))R^(f2), 7) —SO₂—NR^(e2)R^(f2), 8) —C(═NR^(h2))—NR^(e2)R^(f2), 9) —C(═NR^(h2))NR^(e2)—NR^(e2)R^(f2), 10) —C(═N—OR^(h2))NR^(g2)—NR^(e2)R^(f2), 11) —C(═O)NR^(e2)R^(f2), 12) —C(═O)NR^(e2)OR^(f2), 13) —C(═O)NR^(g2)—NR^(e2)R^(f2), 14) —C(═O)R^(e2), and 15) —C(═N—OR^(h2))NR^(e2)R^(f2).
 82. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 3, 11 to 36, 66 to 76, and 81, wherein R⁵ is 5- or 6-membered aryl or heteroaryl selected from the group consisting of

subscript d is the number of substitutable positions on a ring of R⁵, each R^(6a) is independently selected from the group consisting of 1) a hydrogen atom, 2) a hydroxyl group, 3) halogen, 4) a C₁₋₄ alkyl group (wherein the alkyl group is optionally substituted with NR^(e2)R^(f2), a 5- or 6-membered non-aryl heterocycle, —C(═O)OR^(f2), or a hydroxyl group), 5) a C₁₋₄ alkoxy group, 6) —NR^(e2)R^(f2), and 7) —C(═O)OR^(e2), and each R^(6b) is independently selected from the group consisting of 1) a hydrogen atom, 2) a hydroxyl group, and 3) a C₁₋₄ alkyl group (wherein the alkyl group is optionally substituted with NR^(e2)R^(f2), —C(═O)NR^(e2)R^(f2), —C(═O)OR^(f2), or a hydroxyl group).
 83. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 3, 11 to 36, 66 to 76, and 81 to 82, wherein R⁵ is


84. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 3, 11 to 36, 66 to 76, and 81 to 82, wherein R^(e2) and R^(f2) are the same or different, each independently a hydrogen atom, an optionally substituted C₁₋₆ alkyl group, or an optionally substituted C₃₋₁₀ alicyclic group.
 85. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 3, 11 to 36, 66 to 76, 81 to 82, and 84, wherein R^(e2) and R^(f2) are the same or different, each independently a hydrogen atom or an optionally substituted C₁₋₆ alkyl group.
 86. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 3, 11 to 36, 66 to 76, 81 to 82, and 84 to 85, wherein R^(e2) and R^(f2) are hydrogen atoms.
 87. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 81 to 82 and 84 to 85, wherein Ra is —NR^(e2)R^(f2), and one of R^(e2) and R^(f2) is a hydrogen atom and the other is a C₁₋₄ alkyl group (wherein the alkyl group is optionally substituted with an amino group or a hydroxyl group).
 88. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 3, 11 to 36, 66 to 74, and 77, wherein R⁵ is a 4- to 6-membered non-aryl heterocycle selected from the group consisting of

subscript d is the number of substitutable positions on a ring of R⁵, each R⁷ is independently selected from the group consisting of 1) a hydrogen atom, 2) a hydroxyl group, 3) a cyano group, 4) halogen, 5) a C₁₋₄ alkyl group, 6) a C₃₋₁₀ alicyclic group, 7) a C₁₋₄ alkoxy group, 8) a C₃₋₁₀ alicyclic oxy group, 9) a C₆₋₁₀ aryloxy group, 10) a 5- or 6-membered heteroaryloxy group, 11) a 4- to 10-membered non-aryl heterocyclyl oxy group, (wherein each substituent from 5) and 11) is optionally substituted), 12) —SO₂—NR^(e3)R^(f3), 13) —NR^(g2)—CR^(e3)(═NR^(f3)), 14) —NR^(g2)—CR^(e3)(═N—OR^(f3)), 15) —NR^(h2)—C(═NR^(g2))NR^(e3)R^(f3), 16) —NR^(h2)—C(═N—OR^(g2))NR^(e3)R^(f3), 17) —NR^(i2)—C(═NR^(h2))NR^(g2)—NR^(e3)R^(f3), 18) —NR^(i2)—C(═N—OR^(h2))NR^(g2)—NR^(e3)R^(f3), 19) —C(═NR^(e3))R^(f3), 20) —C(═N—OR^(e3))R^(f3), 21) —C(═NR^(h2))—NR^(e3)R^(f3), 22) —C(═NR^(h2))NR^(g2)—NR^(e3)R^(f3), 23) —C(═N—OR^(h2))NR^(g2)—NR^(e3)R^(f3), 24) —NR^(e3)R^(f3), 25) —NR^(g2)—NR^(e3)R^(f3), 26) —NR^(e3)OR^(f3), 27) —NR^(e3)—C(═O)R^(f3), 28) —C(═O)NR^(e3)R^(f3), 29) —C(═O)NR^(e3)OR^(f3), 30) —C(═O)NR^(g2)—NR^(e3)R^(f3), 31) —C(═O)R^(e3), 32) —C(═O)OR^(e3), and 33) —C(═N—OR^(h2))NR^(e3)R^(f3), each R^(7b) is independently selected from the group consisting of 1) a hydrogen atom, 2) a hydroxyl group, 3) a C₁₋₄ alkyl group (wherein the alkyl group is optionally substituted), 4) a C₃₋₁₀ alicyclic group (wherein the alicyclic group is optionally substituted), 5) —C(═NR^(e3))R^(f3), 6) —C(═N—OR^(e3))R^(f3), 7) —SO₂—NR^(e3)R^(f3), 8) —C(═NR^(h2))NR^(e3)R^(f3), 9) —C(═NR^(h2))—NR^(g2)—R^(e3)R^(f3), 10) —C(═N—OR^(h2))NR^(g2)—NR^(e3)R^(f3), 11) —C(═O)NR^(e3)R^(f3), 12) —C(═O)NR^(e3)OR^(f3), 13) —C(═O)NR^(g2)—NR^(e3)R^(f3), 14) —C(═O)R^(e3), and 15) —C(═N—OR^(h2))NR^(e3)R^(f3), and R^(e3), R^(f3), R^(g2), R^(h2), and R^(i2) are defined the same as R^(e2), R^(f2), R^(g2), R^(h2), and R^(i2) according to claim
 3. 89. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 3, 11 to 36, 66 to 74, 77, and 88, wherein R⁵ is a 4- to 6-membered non-aryl heterocycle selected from the group consisting of

subscript d is the number of substitutable positions on a ring of R⁵, each R^(7a) is independently selected from the group consisting of 1) a hydrogen atom, 2) a hydroxyl group, 3) halogen, 4) a C₁₋₄ alkyl group (wherein the alkyl group is optionally substituted with NR^(e3)R^(f3), a 5- or 6-membered non-aryl heterocycle, —C(═O)OR^(f3), or a hydroxyl group), 5) a C₁₋₄ alkoxy group, 6) —NR^(e3)R^(f3), 7) —C(═O)OR^(e3), 8) C₆₋₁₀ aryl, and 9) —C(═O)NR^(e3)R^(f3), each R^(7b) is independently selected from the group consisting of 1) a hydrogen atom, 2) a hydroxyl group, and 3) a C₁₋₄ alkyl group (wherein the alkyl group is optionally substituted with NR^(e3)R^(f3), —C(═O)OR³, or a hydroxyl group), and R^(e3) and R^(f3) are defined the same as R^(e2) and R^(f2) according to any one of claims 84 to
 86. 90. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 3, 11 to 36, 66 to 74, and 77, wherein R⁵ is C₄₋₆ cycloalkyl selected from the group consisting of

subscript d is the number of substitutable positions on a ring of R⁵, each R^(9a) is independently selected from the group consisting of 1) a hydrogen atom, 2) a hydroxyl group, 3) a cyano group, 4) halogen, 5) a C₁₋₄ alkyl group, 6) a C₃₋₁₀ alicyclic group, 7) a C₁₋₄ alkoxy group, 8) a C₃₋₁₀ alicyclic oxy group, 9) a C₆₋₁₀ aryloxy group, 10) a 5- or 6-membered heteroaryloxy group, 11) a 4- to 10-membered non-aryl heterocyclyl oxy group, (wherein each substituent from 5) and 11) is optionally substituted), 12) —SO₂—NR^(e3)R^(f3), 13) —NR^(g2)—CR^(e3)(═NR^(f3)), 14) —NR^(g2)—CR^(e3)(═N—OR^(f3)), 15) —NR^(h2)—C(═NR^(g2))NR^(e3)R^(f3), 16) —NR^(h2)—C(═N—OR^(g2))NR^(e3)R^(f3), 17) —NR^(i2)—C(═NR^(h2))NR^(g2)—NR^(e3)R^(f3), 18) —NR^(i2)—C(═N—OR^(h2))NR^(g2)—NR^(e3)R^(f3), 19) —C(═NR^(e3))R^(f3), 20) —C(═N—OR^(e3))R^(f3), 21) —C(═NR^(h2))—NR^(e3)R^(f3), 22) —C(═NR^(h2))NR^(g2)—NR^(e3)R^(f3), 23) —C(═N—OR^(h2))NR^(g2)—NR^(e3)R^(f3), 24) —NR^(e3)R^(f3), 25) —NR^(g2)—NR^(e3)R^(f3), 26) —NR^(e3)OR^(f3), 27) —NR^(e3)—C(═O)R^(f3), 28) —C(═O)NR^(e3)R^(f3), 29) —C(═O)NR^(e3)OR^(f3), 30) —C(═O)NR^(g2)—NR^(e3)R^(f3), 31) —C(═O)R^(e3), 32) —C(═O)OR^(e3), and 33) —C(═N—OR^(h2))NR^(e3)R^(f3), and R^(e3), R^(f3), R^(g2), R^(h2), and R^(i2) are defined the same as R^(e2) and R^(f2) according to claim
 3. 91. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 3, 11 to 36, 66 to 74, 77, and 90, wherein R⁵ is C₄₋₆ cycloalkyl selected from the group consisting of

subscript d is the number of substitutable positions on a ring of R⁵, each R^(9a) is independently selected from the group consisting of 1) a hydrogen atom, 2) a hydroxyl group, 3) halogen, 4) a C₁₋₄ alkyl group (wherein the alkyl group is optionally substituted with NR^(e3)R^(f3), a 5- or 6-membered non-aryl heterocycle, —C(═O)OR^(f3), or a hydroxyl group), 5) a C₁₋₄ alkoxy group, 6) —NR^(e3)R^(f3), 7) —C(═O)OR^(e3), 8) C₆₋₁₀ aryl, and 9) —C(═O)NR^(e3)R^(f3), and R^(e3) and R^(f3) are defined the same as R^(e2) and R^(f2) according to any one of claims 75 to
 77. 92. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 3, 11 to 36, and 79 to 80, wherein L⁴ is —CH(NH₂)—CHR¹³—, wherein carbon that attaches to the NH₂ attaches to L³, R⁵ is a hydrogen atom, and R¹³ is 1) —NH—C(═O) CH₃, 2) —NH—C(═O)NH₂, 3) —NH—C(═O)CH(NH₂)—CH₂C(═O)NH₂, 4) —NH—C(═O) CH₂—NH₂, 5) —NH—C(═O)CH(NH₂)—CH₂OH, or 6) a pyrrolidin-2-ylcarbonylamino group.
 93. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 3, 11 to 36, and 79 to 80, wherein L⁴ is —CH(NH₂)—CR²R³—, wherein carbon that attaches to the NH₂ attaches to L³, R⁵ is a hydrogen atom or methyl, R¹² is a hydrogen atom or methyl, and R¹³ is a benzylthio group or a sulfanyl group.
 94. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 3, 11 to 36, and 79 to 80, wherein L⁴ is —CH(NH₂)—(CH₂)_(q)—CHR³—, wherein q is 0 or 1, and carbon that attaches to the NH₂ attaches to L³, R⁵ is a hydrogen atom, and R¹³ is 1) a carboxyl group, 2) —C(═O)NH₂, 3) —C(═O)NH(CH₃), 4) —C(═O)N(CH₃)₂, 5) —C(═O)NH—(CH₂)₂—OH, 6) —C(═O)NH—(CH₂)₂—NH₂, 7) —C(═O)NH—S(═O)₂—CH₃, 8) —C(═O)NHOH, 9) —S(═O)₂—NH₂, 10) —S(═O)₂—CH₃, or 11) a hydroxyl group.
 95. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 3, 11 to 36, and 79 to 80, wherein L⁴ is —CH(NHR¹¹)—CH₂—, wherein carbon that attaches to the NHR¹¹ attaches to L³, R⁵ is hydrogen, and R¹¹ is 1) —C(═O)CH(NH₂)—CH₂C(═O)NH₂, 2) —C(═O)CH₂—NH₂, 3) —C(═O)CH(CH₃)—NH₂, 4) —C(═O)CH(NH₂)—CH₂OH, or 5) pyrrolidin-2-ylcarbonyl.
 96. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 3, 11 to 36, and 79 to 80, wherein L⁴ is —CH(NHR¹¹)—CH(COOH)—, wherein carbon that attaches to the NHR¹¹ attaches to L³, R⁵ is hydrogen, and R¹¹ is 1) —C(═O)CH(NH₂)—CH₂C(═O)NH₂, 2) —C(═O)CH₂—NH₂, 3) —C(═O)CH(CH₃)—NH₂, 4) —C(═O)CH(NH₂)—CH₂OH, or 5) pyrrolidin-2-ylcarbonyl.
 97. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 3, 11 to 36, and 79 to 80, wherein L⁴ is —CHR¹³— or —CH₂—CHR¹³—, R⁵ is hydrogen, and R¹³ is —C(═O)NH₂ or —C(═O)NHOH.
 98. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 3, 11 to 36, and 79 to 80, wherein L⁴ is —CH₂—CR¹⁰(NH₂)—, wherein the CH₂ group attaches to L³, R⁵ is hydrogen, and R¹⁰ is a carboxy group or —C(═O)NH₂.
 99. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 3, 11 to 36, and 79 to 80, wherein L⁴ is —(CH₂)_(p)—CR¹⁰(NHR¹¹)—(CH₂)_(q)—CHR¹³— or —CHR¹³—(CH₂)_(q)—CR¹⁰(NHR¹¹)—(CH₂)_(p)—, wherein q is 0 or 1, R⁵ is hydrogen, (1) if L⁴ is —CHR³—(CH₂)_(q)—CR¹⁰(NHR¹¹)—(CH₂)_(p)—, carbon of the —CHR¹³— group attaches to L³, p is 0, R¹⁰ is a hydrogen atom, a carboxyl group, or —C(═O)NHR^(10b), R¹¹ is a hydrogen atom, R^(10b) is a hydrogen atom, wherein if R¹⁰ is —C(═O)NHR^(10b), R^(10b) and R¹¹ together may form —CH₂CH₂—, and R¹³ is a hydrogen atom, (2) if L⁴ is —(CH₂)_(p)—CR¹⁰(NHR¹¹)—(CH₂)_(q)—CHR¹³, carbon of the —(CH₂)_(p)— group attaches to L³, p is 1, R¹⁰ and R¹¹ are both hydrogen atoms, R¹³ is a carboxyl group or —C(═O)NR^(13a)R^(13b), and R^(13a) and R^(13b) are each independently a hydrogen atom or an optionally substituted C₁₋₄ alkyl group.
 100. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 3, 11 to 36, and 79 to 80, wherein L⁴ is —CR¹²(NH₂)—, R² is a hydrogen atom or a methyl group, and R⁵ is a C₁₋₄ alkyl group optionally substituted with a hydroxyl group.
 101. The compound or the pharmaceutically acceptable salt thereof according to claim 1 or 2, selected from the group consisting of the compounds represented by the following names or structural formulas: 5-({1-[amino(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

9-[1-[2-amino-2-(1H-imidazol-4-yl)acetyl]azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid

(1aS,7bR)-5-({1-[(2R)-2-amino-2-(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2R,4S)-9-[1-[(2R)-2-amino-2-(1H-imidazol-4-yl)acetyl]azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid

(1aS,7bR)-5-({1-[(2S)-2-amino-2-(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2R,4S)-9-[1-[(2S)-2-amino-2-(1H-imidazol-4-yl)acetyl]azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid

(1aR,7bS)-5-({1-[(2R)-2-amino-2-(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2S,4R)-9-[1-[(2R)-2-amino-2-(1H-imidazol-4-yl)acetyl]azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid

(1aR,7bS)-5-({1-[(2S)-2-amino-2-(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2S,4R)-9-[1-[(2S)-2-amino-2-(1H-imidazol-4-yl)acetyl]azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid

5-({1-(2-amino-2-carboxypropyl)azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

9-[1-(propyl 2-amino-2-carboxylate)azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

(1aS,7bR)-5-({1-[(2R)-2-amino-2-carboxypropyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2R,4S)-9-[1-[propyl (2R)-2-amino-2-carboxylate]azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

(1aR,7bS)-5-({1-[(2R)-2-amino-2-carboxypropyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2S,4R)-9-[1-[propyl (2R)-2-amino-2-carboxylate]azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

5-({1-[2-amino-2-(1H-imidazol-4-yl)propanoyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

9-[1-[2-amino-2-(1H-imidazol-4-yl)propanoyl]azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid

(1aS,7bR)-5-({1-[(2R)-2-amino-2-(1H-imidazol-4-yl)propanoyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2R,4S)-9-[1-[(2R)-2-amino-2-(1H-imidazol-4-yl)propanoyl]azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid

(1aS,7bR)-5-({1-[(2S)-2-amino-2-(1H-imidazol-4-yl)propanoyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2R,4S)-9-[1-[(2S)-2-amino-2-(1H-imidazol-4-yl)propanoyl]azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid

(1aR,7bS)-5-({1-[(2R)-2-amino-2-(1H-imidazol-4-yl)propanoyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2S,4R)-9-[1-[(2R)-2-amino-2-(1H-imidazol-4-yl)propanoyl]azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid

(1aR,7bS)-5-({1-[(2S)-2-amino-2-(1H-imidazol-4-yl)propanoyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

and (2S,4R)-9-[1-[(2S)-2-amino-2-(1H-imidazol-4-yl)propanoyl]azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid


102. The compound or the pharmaceutically acceptable salt thereof according to claim 1 or 2, selected from the group consisting of the compounds represented by the following names or structural formulas: 2-hydroxy-5-({1-[(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy)-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

5,5-dihydroxy-9-{1-[(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid

(1aS,7bR)-2-hydroxy-5-({1-[(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy)-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2R,4S)-5,5-dihydroxy-9-{1-[(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid

(1aR,7bS)-2-hydroxy-5-({1-[(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy)-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2S,4R)-5,5-dihydroxy-9-{1-[(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid

2-hydroxy-5-[(1-serylazetidin-3-yl)oxy]-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

5,5-dihydroxy-9-(1-serylazetidin-3-yl)oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid

(1aS,7bR)-2-hydroxy-5-[(1-D-serylazetidin-3-yl)oxy]-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2R,4S)-5,5-dihydroxy-9-(1-D-serylazetidin-3-yl)oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid

(1aS,7bR)-2-hydroxy-5-[(1-L-serylazetidin-3-yl)oxy]-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2R,4S)-5,5-dihydroxy-9-(1-L-serylazetidin-3-yl)oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid

(1aR,7bS)-2-hydroxy-5-[(1-D-serylazetidin-3-yl)oxy]-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2S,4R)-5,5-dihydroxy-9-(1-D-serylazetidin-3-yl)oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid

(1aR,7bS)-2-hydroxy-5-[(1-L-serylazetidin-3-yl)oxy]-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2S,4R)-5,5-dihydroxy-9-(1-L-serylazetidin-3-yl)oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid

2-hydroxy-5-({1-[4-hydroxy-prolyl]azetidin-3-yl}oxy)-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

5,5-dihydroxy-9-{1-[4-hydroxy-prolyl]azetidin-3-yl}oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid

(1aS,7bR)-2-hydroxy-5-({1-[(4R)-4-hydroxy-L-prolyl]azetidin-3-yl}oxy)-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2R,4S)-5,5-dihydroxy-9-{1-[(4R)-4-hydroxy-L-prolyl]azetidin-3-yl}oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid

(1aS,7bR)-2-hydroxy-5-({1-[(4S)-4-hydroxy-L-prolyl]azetidin-3-yl}oxy)-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2R,4S)-5,5-dihydroxy-9-{1-[(4S)-4-hydroxy-L-prolyl]azetidin-3-yl}oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid

(1aS,7bR)-2-hydroxy-5-({1-[(4R)-4-hydroxy-D-prolyl]azetidin-3-yl}oxy)-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2R,4S)-5,5-dihydroxy-9-{1-[(4R)-4-hydroxy-D-prolyl]azetidin-3-yl}oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid

(1aS,7bR)-2-hydroxy-5-({1-[(4S)-4-hydroxy-D-prolyl]azetidin-3-yl}oxy)-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2R,4S)-5,5-dihydroxy-9-{1-[(4S)-4-hydroxy-D-prolyl]azetidin-3-yl}oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid

(1aR,7bS)-2-hydroxy-5-({1-[(4R)-4-hydroxy-L-prolyl]azetidin-3-yl}oxy)-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2S,4R)-5,5-dihydroxy-9-{1-[(4R)-4-hydroxy-L-prolyl]azetidin-3-yl}oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid

(1aR,7bS)-2-hydroxy-5-({1-[(4S)-4-hydroxy-L-prolyl]azetidin-3-yl}oxy)-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2S,4R)-5,5-dihydroxy-9-{1-[(4S)-4-hydroxy-L-prolyl]azetidin-3-yl}oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid

(1aS,7bR)-2-hydroxy-5-({1-[(4R)-4-hydroxy-D-prolyl]azetidin-3-yl}oxy)-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2S,4R)-5,5-dihydroxy-9-{1-[(4R)-4-hydroxy-D-prolyl]azetidin-3-yl}oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid

(1aR,7bS)-2-hydroxy-5-({1-[(4S)-4-hydroxy-D-prolyl]azetidin-3-yl}oxy)-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2S,4R)-5,5-dihydroxy-9-{1-[(4S)-4-hydroxy-D-prolyl]azetidin-3-yl}oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid

2-hydroxy-5-{[1-(2-methyl-seryl)azetidin-3-yl]oxy}-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

5,5-dihydroxy-9-[1-(2-methyl-seryl)azetidin-3-yl]oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid

(1aS,7bR)-2-hydroxy-5-{[1-(2-methyl-D-seryl)azetidin-3-yl]oxy}-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2R,4S)-5,5-dihydroxy-9-[1-(2-methyl-D-seryl)azetidin-3-yl]oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid

(1aS,7bR)-2-hydroxy-5-{[1-(2-methyl-L-seryl)azetidin-3-yl]oxy}-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2R,4S)-5,5-dihydroxy-9-[1-(2-methyl-L-seryl)azetidin-3-yl]oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid

(1aR,7bS)-2-hydroxy-5-{[1-(2-methyl-D-seryl)azetidin-3-yl]oxy}-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2S,4R)-5,5-dihydroxy-9-[1-(2-methyl-D-seryl)azetidin-3-yl]oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid

(1aR,7bS)-2-hydroxy-5-{[1-(2-methyl-L-seryl)azetidin-3-yl]oxy}-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2S,4R)-5,5-dihydroxy-9-[1-(2-methyl-L-seryl)azetidin-3-yl]oxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid

2-hydroxy-5-[(1-{[morpholin-2-yl]acetyl}azetidin-3-yl)oxy]-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

5,5-dihydroxy-9-(1-{[morpholin-2-yl]acetyl}azetidin-3-yl)oxy-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid

(1aS,7bR)-2-hydroxy-5-[(1-{[(2R)-morpholin-2-yl]acetyl}azetidin-3-yl)oxy]-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2R,4S)-5,5-dihydroxy-9-(1-{[(2R)-morpholin-2-yl]acetyl}azetidin-3-yl)oxy-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid

(1aS,7bR)-2-hydroxy-5-[(1-{[(2S)-morpholin-2-yl]acetyl}azetidin-3-yl)oxy]-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2S,4R)-5,5-dihydroxy-9-(1-{[(2R)-morpholin-2-yl]acetyl}azetidin-3-yl)oxy-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid

(1aR,7bS)-2-hydroxy-5-[(1-{[(2R)-morpholin-2-yl]acetyl}azetidin-3-yl)oxy]-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2S,4R)-5,5-dihydroxy-9-(1-{[(2R)-morpholin-2-yl]acetyl}azetidin-3-yl)oxy-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid

(1aR,7bS)-2-hydroxy-5-[(1-{[(2S)-morpholin-2-yl]acetyl}azetidin-3-yl)oxy]-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2S,4R)-5,5-dihydroxy-9-(1-{[(2S)-morpholin-2-yl]acetyl}azetidin-3-yl)oxy-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid

(1aS,7bR)-5-({1-[(2S)-2-amino-2-carboxypropyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2R,4S)-9-[1-[propyl (2S)-2-amino-2-carboxylate]azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

(1aR,7bS)-5-({1-[(2S)-2-amino-2-carboxypropyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2S,4R)-9-[1-[propyl (2S)-2-amino-2-carboxylate]azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

5-({1-[2-amino-2-carboxypropyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

9-(1-{2-amino-3-[(2-hydroxyethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

(1aS,7bR)-5-[(1-{(2R)-2-amino-3-[(2-hydroxyethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2R,4S)-9-(1-{(2R)-2-amino-3-[(2-hydroxyethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

(1aS,7bR)-5-[(1-{(2S)-2-amino-3-[(2-hydroxyethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2R,4S)-9-(1-{(2S)-2-amino-3-[(2-hydroxyethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

(1aR,7bS)-5-[(1-{(2R)-2-amino-3-[(2-hydroxyethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2S,4R)-9-(1-{(2R)-2-amino-3-[(2-hydroxyethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

(1aR,7bS)-5-[(1-{(2S)-2-amino-3-[(2-hydroxyethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2S,4R)-9-(1-{(2S)-2-amino-3-[(2-hydroxyethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

5-[(1-{2-amino-3-[(2-amino-2-oxoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

9-(1-{2-amino-3-[(2-amino-2-oxoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

(1aS,7bR)-5-[(1-{(2R)-2-amino-3-[(2-amino-2-oxoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2R,4S)-9-(1-{(2R)-2-amino-3-[(2-amino-2-oxoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

(1aS,7bR)-5-[(1-{(2S)-2-amino-3-[(2-amino-2-oxoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2R,4S)-9-(1-{(2S)-2-amino-3-[(2-amino-2-oxoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

(1aR,7bS)-5-[(1-{(2R)-2-amino-3-[(2-amino-2-oxoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2S,4R)-9-(1-{(2R)-2-amino-3-[(2-amino-2-oxoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

(1aR,7bS)-5-[(1-{(2S)-2-amino-3-[(2-amino-2-oxoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2S,4R)-9-(1-{(2S)-2-amino-3-[(2-amino-2-oxoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

5-({1-[5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

9-{1-[5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

(1aS,7bR)-5-({1-[(3S,5S)-5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2R,4S)-9-{1-[(3S,5S)-5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

(1aS,7bR)-5-({1-[(3R,5S)-5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2R,4S)-9-{1-[(3R,5S)-5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

(1aS,7bR)-5-({1-[(3S,5R)-5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2R,4S)-9-{1-[(3S,5R)-5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

(1aS,7bR)-5-({1-[(3R,5R)-5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2R,4S)-9-{1-[(3R,5R)-5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

(1aR,7bS)-5-({1-[(3S,5S)-5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2S,4R)-9-{1-[(3S,5S)-5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

(1aR,7bS)-5-({1-[(3R,5S)-5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2S,4R)-9-{1-[(3R,5S)-5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

(1aR,7bS)-5-({1-[(3S,5R)-5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2S,4R)-9-{1-[(3S,5R)-5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

(1aR,7bS)-5-({1-[(3R,5R)-5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2S,4R)-9-{1-[(3R,5R)-5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

5-{[1-(2-amino-2-oxoethyl)azetidin-3-yl]oxy}-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

9-[1-(2-amino-2-oxoethyl)azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

(1aS,7bR)-5-{[1-(2-amino-2-oxoethyl)azetidin-3-yl]oxy}-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2R,4S)-9-[1-(2-amino-2-oxoethyl)azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

(1aR,7bS)-5-{[1-(2-amino-2-oxoethyl)azetidin-3-yl]oxy}-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2S,4R)-9-[1-(2-amino-2-oxoethyl)azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

2-hydroxy-5-[(1-{2-[(2-hydroxyethoxy)amino]-2-oxoethyl}azetidin-3-yl)oxy]-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

5,5-dihydroxy-9-(1-{2-[(2-hydroxyethoxy)amino]-2-oxoethyl}azetidin-3-yl)oxy-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid

(1aS,7bR)-2-hydroxy-5-[(1-{2-[(2-hydroxyethoxy)amino]-2-oxoethyl}azetidin-3-yl)oxy]-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2R,4S)-5,5-dihydroxy-9-(1-{2-[(2-hydroxyethoxy)amino]-2-oxoethyl}azetidin-3-yl)oxy-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid

(1aR,7bS)-2-hydroxy-5-[(1-{2-[(2-hydroxyethoxy)amino]-2-oxoethyl}azetidin-3-yl)oxy]-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2S,4R)-5,5-dihydroxy-9-(1-{2-[(2-hydroxyethoxy)amino]-2-oxoethyl}azetidin-3-yl)oxy-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid

5-({1-[2-amino-3-hydroxy-2-(hydroxymethyl)propyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

9-{1-[2-amino-3-hydroxy-2-(hydroxymethyl)propyl]azetidin-3-yl}oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

(1aS,7bR)-5-({1-[2-amino-3-hydroxy-2-(hydroxymethyl)propyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2R,4S)-9-{1-[2-amino-3-hydroxy-2-(hydroxymethyl)propyl]azetidin-3-yl}oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

(1aR,7bS)-5-({1-[2-amino-3-hydroxy-2-(hydroxymethyl)propyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2S,4R)-9-{1-[2-amino-3-hydroxy-2-(hydroxymethyl)propyl]azetidin-3-yl}oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

5-({1-[(1-aminocyclopropyl)methyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

9-{1-[(1-aminocyclopropyl)methyl]azetidin-3-yl}oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

(1aS,7bR)-5-({1-[(1-aminocyclopropyl)methyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2R,4S)-9-{1-[(1-aminocyclopropyl)methyl]azetidin-3-yl}oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

(1aR,7bS)-5-({1-[(1-aminocyclopropyl)methyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2S,4R)-9-{1-[(1-aminocyclopropyl)methyl]azetidin-3-yl}oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

2-hydroxy-5-({1-[(1H-1,2,4-triazol-3-yl)methyl]azetidin-3-yl}oxy)-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

5,5-dihydroxy-9-{1-[(1H-1,2,4-triazol-3-yl)methyl]azetidin-3-yl}oxy-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid

(1aS,7bR)-2-hydroxy-5-({1-[(1H-1,2,4-triazol-3-yl)methyl]azetidin-3-yl}oxy)-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2R,4S)-5,5-dihydroxy-9-{1-[(1H-1,2,4-triazol-3-yl)methyl]azetidin-3-yl}oxy-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid

(1aR,7bS)-2-hydroxy-5-({1-[(1H-1,2,4-triazol-3-yl)methyl]azetidin-3-yl}oxy)-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2S,4R)-5,5-dihydroxy-9-{1-[(1H-1,2,4-triazol-3-yl)methyl]azetidin-3-yl}oxy-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid

5-{[1-({4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy}-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

9-[1-({4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

(1aS,7bR)-5-{[1-({(1r,4r)-4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy}-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2R,4S)-9-[1-({(1r,4r)-4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

(1aS,7bR)-5-{[1-({(1s,4r)-4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy}-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2R,4S)-9-[1-({(1s,4r)-4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

(1aS,7bR)-5-{[1-({(1r,4s)-4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy}-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2R,4S)-9-[1-({(1r,4s)-4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0²′ ]undeca-1(7),8,10-triene-8-carboxylate

(1aS,7bR)-5-{[1-({(1s,4s)-4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy}-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2R,4S)-9-[1-({(1s,4s)-4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

(1aR,7bS)-5-{[1-({(1r,4r)-4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy}-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2S,4R)-9-[1-({(1r,4r)-4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

(1aR,7bS)-5-{[1-({(1s,4r)-4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy}-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2S,4R)-9-[1-({(1s,4r)-4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

(1aR,7bS)-5-{[1-({(1r,4s)-4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy}-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2S,4R)-9-[1-({(1r,4s)-4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

(1aR,7bS)-5-{[1-({(1s,4s)-4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy}-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2S,4R)-9-[1-({(1s,4s)-4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

5-[(1-{2-amino-3-[(2-aminoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

9-(1-{2-amino-3-[(2-aminoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

(1aS,7bR)-5-[(1-{(2R)-2-amino-3-[(2-aminoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2R,4S)-9-(1-{(2R)-2-amino-3-[(2-aminoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

(1aS,7bR)-5-[(1-{(2S)-2-amino-3-[(2-aminoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2R,4S)-9-(1-{(2S)-2-amino-3-[(2-aminoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

(1aR,7bS)-5-[(1-{(2R)-2-amino-3-[(2-aminoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2S,4R)-9-(1-{(2R)-2-amino-3-[(2-aminoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

(1aR,7bS)-5-[(1-{(2S)-2-amino-3-[(2-aminoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2S,4R)-9-(1-{(2S)-2-amino-3-[(2-aminoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylate

5-[(1-histidylazetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

9-(1-histidylazetidin-3-yl)oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic acid

(1aS,7bR)-5-[(1-D-histidylazetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2R,4S)-9-(1-D-histidylazetidin-3-yl)oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic acid

(1aS,7bR)-5-[(1-L-histidylazetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2R,4S)-9-(1-L-histidylazetidin-3-yl)oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic acid

(1aR,7bS)-5-[(1-D-histidylazetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2S,4R)-9-(1-D-histidylazetidin-3-yl)oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic acid

(1aR,7bS)-5-[(1-L-histidylazetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2S,4R)-9-(1-L-histidylazetidin-3-yl)oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic acid

5-{[1-(2-aminoethyl)azetidin-3-yl]oxy}-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

9-[1-(2-aminoethyl)azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic acid

(1aS,7bR)-5-{[1-(2-aminoethyl)azetidin-3-yl]oxy}-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2R,4S)-9-[1-(2-aminoethyl)azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic acid

(1aR,7bS)-5-{[1-(2-aminoethyl)azetidin-3-yl]oxy}-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2S,4R)-9-[1-(2-aminoethyl)azetidin-3-yl]oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic acid

5-[(1-{[5-(aminomethyl)morpholin-2-yl]acetyl}azetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

9-(1-{[5-(aminomethyl)morpholin-2-yl]acetyl}azetidin-3-yl)oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic acid

(1aS,7bR)-5-[(1-{[5-(aminomethyl)morpholin-2-yl]acetyl}azetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2R,4S)-9-(1-{[5-(aminomethyl)morpholin-2-yl]acetyl}azetidin-3-yl)oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic acid

(1aR,7bS)-5-[(1-{[5-(aminomethyl)morpholin-2-yl]acetyl}azetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2S,4R)-9-(1-{[5-(aminomethyl)morpholin-2-yl]acetyl}azetidin-3-yl)oxy-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic acid

5-({1-[2-amino-2-methyl-3-{[2-(methylamino)-2-oxoethyl]amino}-3-oxopropyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

9-({1-[2-amino-2-methyl-3-{[2-(methylamino)-2-oxoethyl]amino}-3-oxopropyl]azetidin-3-yl}oxy)-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic acid

(1aS,7bR)-5-({1-[(2R)-2-amino-2-methyl-3-{[2-(methylamino)-2-oxoethyl]amino}-3-oxopropyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2R,4S)-9-({1-[(2R)-2-amino-2-methyl-3-{[2-(methylamino)-2-oxoethyl]amino}-3-oxopropyl]azetidin-3-yl}oxy)-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0²′ ]undeca-1(7),8,10-triene-8-carboxylic acid

(1aS,7bR)-5-({1-[(2S)-2-amino-2-methyl-3-{[2-(methylamino)-2-oxoethyl]amino}-3-oxopropyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2R,4S)-9-({1-[(2S)-2-amino-2-methyl-3-{[2-(methylamino)-2-oxoethyl]amino}-3-oxopropyl]azetidin-3-yl}oxy)-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic acid

(1aR,7bS)-5-({1-[(2R)-2-amino-2-methyl-3-{[2-(methylamino)-2-oxoethyl]amino}-3-oxopropyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2S,4R)-9-({1-[(2R)-2-amino-2-methyl-3-{[2-(methylamino)-2-oxoethyl]amino}-3-oxopropyl]azetidin-3-yl}oxy)-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic acid

(1aR,7bS)-5-({1-[(2S)-2-amino-2-methyl-3-{[2-(methylamino)-2-oxoethyl]amino}-3-oxopropyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2S,4R)-9-({1-[(2S)-2-amino-2-methyl-3-{[2-(methylamino)-2-oxoethyl]amino}-3-oxopropyl]azetidin-3-yl}oxy)-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic acid

5-({1-[2-amino-3-{[2-(dimethylamino)-2-oxoethyl]amino}-2-methyl-3-oxopropyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

9-({1-[2-amino-3-{[2-(dimethylamino)-2-oxoethyl]amino}-2-methyl-3-oxopropyl]azetidin-3-yl}oxy)-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic acid

(1aS,7bR)-5-({1-[(2R)-2-amino-3-{[2-(dimethylamino)-2-oxoethyl]amino}-2-methyl-3-oxopropyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2R,4S)-9-({1-[(2R)-2-amino-3-{[2-(dimethylamino)-2-oxoethyl]amino}-2-methyl-3-oxopropyl]azetidin-3-yl}oxy)-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic acid

(1aS,7bR)-5-({1-[(2S)-2-amino-3-{[2-(dimethylamino)-2-oxoethyl]amino}-2-methyl-3-oxopropyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2R,4S)-9-({1-[(2S)-2-amino-3-{[2-(dimethylamino)-2-oxoethyl]amino}-2-methyl-3-oxopropyl]azetidin-3-yl}oxy)-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic acid

(1aR,7bS)-5-({1-[(2R)-2-amino-3-{[2-(dimethylamino)-2-oxoethyl]amino}-2-methyl-3-oxopropyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2S,4R)-9-({1-[(2R)-2-amino-3-{[2-(dimethylamino)-2-oxoethyl]amino}-2-methyl-3-oxopropyl]azetidin-3-yl}oxy)-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0²′ ]undeca-1(7),8,10-triene-8-carboxylic acid

(1aR,7bS)-5-({1-[(2S)-2-amino-3-{[2-(dimethylamino)-2-oxoethyl]amino}-2-methyl-3-oxopropyl]azetidin-3-yl}oxy)-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2S,4R)-9-({1-[(2S)-2-amino-3-{[2-(dimethylamino)-2-oxoethyl]amino}-2-methyl-3-oxopropyl]azetidin-3-yl}oxy)-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic acid

2-hydroxy-5-[(1-{[4-methylmorpholin-2-yl]acetyl}azetidin-3-yl)oxy]-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

5,5-dihydroxy-9-[(1-{[(4-methylmorpholin-2-yl]acetyl}azetidin-3-yl)oxy]-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid

(1aS,7bR)-2-hydroxy-5-[(1-{[(2R)-4-methylmorpholin-2-yl]acetyl}azetidin-3-yl)oxy]-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2R,4S)-5,5-dihydroxy-9-[(1-{[(2R)-4-methylmorpholin-2-yl]acetyl}azetidin-3-yl)oxy]-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid

(1aS,7bR)-2-hydroxy-5-[(1-{[(2S)-4-methylmorpholin-2-yl]acetyl}azetidin-3-yl)oxy]-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2R,4S)-5,5-dihydroxy-9-[(1-{[(2S)-4-methylmorpholin-2-yl]acetyl}azetidin-3-yl)oxy]-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid

(1aR,7bS)-2-hydroxy-5-[(1-{[(2R)-4-methylmorpholin-2-yl]acetyl}azetidin-3-yl)oxy]-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2S,4R)-5,5-dihydroxy-9-[(1-{[(2R)-4-methylmorpholin-2-yl]acetyl}azetidin-3-yl)oxy]-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid

(1aR,7bS)-2-hydroxy-5-[(1-{[(2S)-4-methylmorpholin-2-yl]acetyl}azetidin-3-yl)oxy]-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2S,4R)-5,5-dihydroxy-9-[(1-{[(2R)-4-methylmorpholin-2-yl]acetyl}azetidin-3-yl)oxy]-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid

5-[(1-{[4,4-dimethylmorpholin-4-ium-2-yl]acetyl}azetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylate

9-[(1-{[4,4-dimethylmorpholin-4-ium-2-yl]acetyl}azetidin-3-yl)oxy]-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic acid

(1aS,7bR)-5-[(1-{[(2R)-4,4-dimethylmorpholin-4-ium-2-yl]acetyl}azetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylate

(2R,4S)-9-[(1-{[(2R)-4,4-dimethylmorpholin-4-ium-2-yl]acetyl}azetidin-3-yl)oxy]-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic acid

(1aS,7bR)-5-[(1-{[(2S)-4,4-dimethylmorpholin-4-ium-2-yl]acetyl}azetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylate

(2R,4S)-9-[(1-{[(2S)-4,4-dimethylmorpholin-4-ium-2-yl]acetyl}azetidin-3-yl)oxy]-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic acid

(1aR,7bS)-5-[(1-{[(2R)-4,4-dimethylmorpholin-4-ium-2-yl]acetyl}azetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylate

(2S,4R)-9-[(1-{[(2R)-4,4-dimethylmorpholin-4-ium-2-yl]acetyl}azetidin-3-yl)oxy]-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic acid

(1aR,7bS)-5-[(1-{[(2S)-4,4-dimethylmorpholin-4-ium-2-yl]acetyl}azetidin-3-yl)oxy]-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylate

(2S,4R)-9-[(1-{[(2S)-4,4-dimethylmorpholin-4-ium-2-yl]acetyl}azetidin-3-yl)oxy]-5,5-dihydroxy-6-oxa-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(7),8,10-triene-8-carboxylic acid

(1aR,7bS)-2-hydroxy-5-({1-[(3-hydroxy-2-methyl-4-oxopyridin-1(4H)-yl)acetyl]azetidin-3-yl}oxy)-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

5,5-dihydroxy-9-({1-[(3-hydroxy-2-methyl-4-oxopyridin-1(4H)-yl) acetyl]azetidin-3-yl}oxy)-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid

(1aR,7bS)-2-hydroxy-5-({1-[(3-hydroxy-2-methyl-4-oxopyridin-1(4H)-yl)acetyl]azetidin-3-yl}oxy)-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

(2S,4R)-5,5-dihydroxy-9-({1-[(3-hydroxy-2-methyl-4-oxopyridin-1(4H)-yl)acetyl]azetidin-3-yl}oxy)-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid

(1aS,7bR)-2-hydroxy-5-({1-[(3-hydroxy-2-methyl-4-oxopyridin-1(4H)-yl)acetyl]azetidin-3-yl}oxy)-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid

and (2R,4S)-5,5-dihydroxy-9-({1-[(3-hydroxy-2-methyl-4-oxopyridin-1(4H)-yl)acetyl]azetidin-3-yl}oxy)-5-boranuidatricyclo[5.4.0.0^(2,4)]undeca-1(11),7,9-triene-8-carboxylic acid


103. A compound represented by formula (11):

or a pharmaceutically acceptable salt thereof, wherein R^(G) is a hydroxyl group, a thiol group, or —NHR^(a1), R^(a1), X, R¹, R², R³, R⁴, R⁶¹, R⁶², R⁶³, and R⁶⁴ are defined the same as the definition according to any of claims 1 to 16, and formula (1a) is defined the same as claim 1 or
 2. 104. The compound or the pharmaceutically acceptable salt thereof according to claim 103, wherein the compound of formula (11) is represented by formula (12):

wherein X, R¹, R², R³, and R⁴ are defined the same as the definition according to claim 17 or
 18. 105. The compound or the pharmaceutically acceptable salt thereof according to claim 103 or 104, wherein the compound of formula (11) or formula (12) is represented by formula (13):

wherein X, Y, ring A, L³, L⁴, R¹, R², R⁴, and R⁵ are defined the same as the definition according to any of claims 19 to 23 and 29 to
 32. 106. The compound or the pharmaceutically acceptable salt thereof according to claim 105, wherein X and R^(G) are hydroxyl groups, R⁴ is a carboxyl group, and ring A is an optionally substituted 4- to 6-membered nitrogen-containing non-aryl heterocycle.
 107. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 103 to 106, wherein the compound of formula (11), formula (12), or formula (13) is represented by formula (14):

wherein X, L³, L⁴, m, n, and R⁵ are defined the same as the definition according to any one of claims 33 to
 64. 108. The compound or the pharmaceutically acceptable salt thereof according to claim 107, wherein the compound of formula (14) is one of the enantiomers represented by formula (15):

and formula (16):

wherein X, L³, L⁴, m, n, and R⁵ are defined the same as the definition according to any one of claims 33 to
 64. 109. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 103 to 108, wherein R^(G) is a hydroxyl group or a thiol group.
 110. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 103 to 109, wherein R^(G) is a hydroxyl group.
 111. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 103 to 110, wherein X is a hydroxyl group or a C₁₋₆ alkoxy group.
 112. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 103 to 111, wherein X is a hydroxyl group.
 113. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 107 to 112, wherein m is 1 or 2, n is 1 or 2, and m+n is 2 or
 3. 114. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 107 to 113, wherein m is 1, and n is
 1. 115. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 103 to 114, wherein L³ is defined the same as the definition according to claim 25 or
 26. 116. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 103 to 115, wherein L⁴ and R³ are defined the same as the definition according to any one of claims 27 and 66 to
 100. 117. The compound or the pharmaceutically acceptable salt thereof according to claim 104, selected from the group consisting of the compounds represented by the following names or structural formulas: 6-({1-[amino(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy)-3-(2-boronocyclopropyl)-2-hydroxybenzoic acid

6-({1-[(2R)-2-amino-2-(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy)-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic acid

6-({1-[(2S)-2-amino-2-(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy)-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic acid

6-({1-[(2R)-2-amino-2-(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy)-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic acid

6-({1-[(2S)-2-amino-2-(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy)-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic acid

6-({1-(2-amino-2-carboxypropyl)azetidin-3-yl}oxy)-3-(2-boronocyclopropyl)-2-hydroxybenzoic acid

6-({1-[(2R)-2-amino-2-carboxypropyl]azetidin-3-yl}oxy)-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic acid

6-({1-[(2R)-2-amino-2-carboxypropyl]azetidin-3-yl}oxy)-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic acid

6-({1-[2-amino-2-(1H-imidazol-4-yl)propanoyl]azetidin-3-yl}oxy)-3-(2-boronocyclopropyl)-2-hydroxybenzoic acid

6-({1-[(2R)-2-amino-2-(1H-imidazol-4-yl)propanoyl]azetidin-3-yl}oxy)-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic acid

6-({1-[(2S)-2-amino-2-(1H-imidazol-4-yl)propanoyl]azetidin-3-yl}oxy)-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic acid

6-({1-[(2R)-2-amino-2-(1H-imidazol-4-yl)propanoyl]azetidin-3-yl}oxy)-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic acid

and 6-({1-[(2S)-2-amino-2-(1H-imidazol-4-yl)propanoyl]azetidin-3-yl}oxy)-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic acid


118. The compound or the pharmaceutically acceptable salt thereof according to claim 104, selected from the group consisting of the compounds represented by the following names or structural formulas: 2-boronocyclopropyl]-2-hydroxy-6-({1-[(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy)benzoic acid

3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxy-6-({1-[(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy)benzoic acid

3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxy-6-({1-[(1H-imidazol-4-yl)acetyl]azetidin-3-yl}oxy)benzoic acid

3-[2-boronocyclopropyl]-2-hydroxy-6-[(1-serylazetidin-3-yl)oxy]benzoic acid

3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxy-6-[(1-D-serylazetidin-3-yl)oxy]benzoic acid

3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxy-6-[(1-L-serylazetidin-3-yl)oxy]benzoic acid

3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxy-6-[(1-D-serylazetidin-3-yl)oxy]benzoic acid

3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxy-6-[(1-L-serylazetidin-3-yl)oxy]benzoic acid

3-[2-boronocyclopropyl]-2-hydroxy-6-({1-[4-hydroxy-L-prolyl]azetidin-3-yl}oxy)benzoic acid

3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxy-6-({1-[(4R)-4-hydroxy-L-prolyl]azetidin-3-yl}oxy)benzoic acid

3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxy-6-({1-[(4S)-4-hydroxy-L-prolyl]azetidin-3-yl}oxy)benzoic acid

3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxy-6-({1-[(4R)-4-hydroxy-D-prolyl]azetidin-3-yl}oxy)benzoic acid

3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxy-6-({1-[(4S)-4-hydroxy-D-prolyl]azetidin-3-yl}oxy)benzoic acid

3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxy-6-({1-[(4R)-4-hydroxy-L-prolyl]azetidin-3-yl}oxy)benzoic acid

3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxy-6-({1-[(4S)-4-hydroxy-L-prolyl]azetidin-3-yl}oxy)benzoic acid

3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxy-6-({1-[(4R)-4-hydroxy-D-prolyl]azetidin-3-yl}oxy)benzoic acid

3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxy-6-({1-[(4S)-4-hydroxy-D-prolyl]azetidin-3-yl}oxy)benzoic acid

3-[2-boronocyclopropyl]-2-hydroxy-6-{[1-(2-methyl-seryl)azetidin-3-yl]oxy}benzoic acid

3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxy-6-{[1-(2-methyl-D-seryl)azetidin-3-yl]oxy}benzoic acid

3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxy-6-{[1-(2-methyl-L-seryl)azetidin-3-yl]oxy}benzoic acid

3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxy-6-{[1-(2-methyl-D-seryl)azetidin-3-yl]oxy}benzoic acid

3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxy-6-{[1-(2-methyl-L-seryl)azetidin-3-yl]oxy}benzoic acid

3-[(2-boronocyclopropyl]-2-hydroxy-6-[(1-{[morpholin-2-yl]acetyl}azetidin-3-yl)oxy]benzoic acid

3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxy-6-[(1-{[(2R)-morpholin-2-yl]acetyl}azetidin-3-yl)oxy]benzoic acid

3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxy-6-[(1-{[(2S)-morpholin-2-yl]acetyl}azetidin-3-yl)oxy]benzoic acid

3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxy-6-[(1-{[(2R)-morpholin-2-yl]acetyl}azetidin-3-yl)oxy]benzoic acid

3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxy-6-[(1-{[(2S)-morpholin-2-yl]acetyl}azetidin-3-yl)oxy]benzoic acid

6-({1-[(2S)-2-amino-2-carboxypropyl]azetidin-3-yl}oxy)-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic acid

6-({1-[(2S)-2-amino-2-carboxypropyl]azetidin-3-yl}oxy)-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic acid

6-[(1-{2-amino-3-[(2-hydroxyethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-3-[2-boronocyclopropyl]-2-hydroxybenzoic acid

6-[(1-{(2R)-2-amino-3-[(2-hydroxyethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic acid

6-[(1-{(2S)-2-amino-3-[(2-hydroxyethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic acid

6-[(1-{(2R)-2-amino-3-[(2-hydroxyethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic acid

6-[(1-{(2S)-2-amino-3-[(2-hydroxyethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic acid

6-[(1-{2-amino-3-[(2-amino-2-oxoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-3-[2-boronocyclopropyl]-2-hydroxybenzoic acid

6-[(1-{(2R)-2-amino-3-[(2-amino-2-oxoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic acid

6-[(1-{(2S)-2-amino-3-[(2-amino-2-oxoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic acid

6-[(1-{(2R)-2-amino-3-[(2-amino-2-oxoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic acid

6-[(1-{(2S)-2-amino-3-[(2-amino-2-oxoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic acid

3-[2-boronocyclopropyl]-6-({1-[(5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy)-2-hydroxybenzoic acid

3-[(1R,2S)-2-boronocyclopropyl]-6-({1-[(3S,5S)-5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy)-2-hydroxybenzoic acid

3-[(1R,2S)-2-boronocyclopropyl]-6-({1-[(3R,5S)-5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy)-2-hydroxybenzoic acid

3-[(1R,2S)-2-boronocyclopropyl]-6-({1-[(3S,5R)-5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy)-2-hydroxybenzoic acid

3-[(1R,2S)-2-boronocyclopropyl]-6-({1-[(3R,5R)-5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy)-2-hydroxybenzoic acid

3-[(1S,2R)-2-boronocyclopropyl]-6-({1-[(3S,5S)-5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy)-2-hydroxybenzoic acid

3-[(1S,2R)-2-boronocyclopropyl]-6-({1-[(3R,5S)-5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy)-2-hydroxybenzoic acid

3-[(1S,2R)-2-boronocyclopropyl]-6-({1-[(3S,5R)-5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy)-2-hydroxybenzoic acid

3-[(1S,2R)-2-boronocyclopropyl]-6-({1-[(3R,5R)-5-carbamoylpyrrolidin-3-yl]azetidin-3-yl}oxy)-2-hydroxybenzoic acid

6-{[1-(2-amino-2-oxoethyl)azetidin-3-yl]oxy}-3-[2-boronocyclopropyl]-2-hydroxybenzoic acid

6-{[1-(2-amino-2-oxoethyl)azetidin-3-yl]oxy}-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic acid

6-{[1-(2-amino-2-oxoethyl)azetidin-3-yl]oxy}-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic acid

3-[(2-boronocyclopropyl]-2-hydroxy-6-[(1-{2-[(2-hydroxyethoxy)amino]-2-oxoethyl}azetidin-3-yl)oxy]benzoic acid

3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxy-6-[(1-{2-[(2-hydroxyethoxy)amino]-2-oxoethyl}azetidin-3-yl)oxy]benzoic acid

3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxy-6-[(1-{2-[(2-hydroxyethoxy)amino]-2-oxoethyl}azetidin-3-yl)oxy]benzoic acid

6-({1-[2-amino-3-hydroxy-2-(hydroxymethyl)propyl]azetidin-3-yl}oxy)-3-[2-boronocyclopropyl]-2-hydroxybenzoic acid

6-({1-[2-amino-3-hydroxy-2-(hydroxymethyl)propyl]azetidin-3-yl}oxy)-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic acid

6-({1-[2-amino-3-hydroxy-2-(hydroxymethyl)propyl]azetidin-3-yl}oxy)-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic acid

6-({1-[(1-aminocyclopropyl)methyl]azetidin-3-yl}oxy)-3-[2-boronocyclopropyl]-2-hydroxybenzoic acid

6-({1-[(1-aminocyclopropyl)methyl]azetidin-3-yl}oxy)-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic acid

6-({1-[(1-aminocyclopropyl)methyl]azetidin-3-yl}oxy)-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic acid

3-[2-boronocyclopropyl]-2-hydroxy-6-({1-[(1H-1,2,4-triazol-3-yl)methyl]azetidin-3-yl}oxy)benzoic acid

3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxy-6-({1-[(1H-1,2,4-triazol-3-yl)methyl]azetidin-3-yl}oxy)benzoic acid

3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxy-6-({1-[(1H-1,2,4-triazol-3-yl)methyl]azetidin-3-yl}oxy)benzoic acid

6-{[1-({4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy}-3-[2-boronocyclopropyl]-2-hydroxybenzoic acid

6-{[1-({(1r,4r)-4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy}-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic acid

6-{[1-({(1s,4r)-4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy}-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic acid

6-{[1-({(1r,4s)-4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy}-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic acid

6-{[1-({(1s,4s)-4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy}-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic acid

6-{[1-({(1r,4r)-4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy}-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic acid

6-{[1-({(1s,4r)-4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy}-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic acid

6-{[1-({(1r,4s)-4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy}-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic acid

6-{[1-({(1s,4s)-4-[(2-aminoethyl)amino]cyclohexyl}acetyl)azetidin-3-yl]oxy}-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic acid

6-[(1-{2-amino-3-[(2-aminoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-3-[2-boronocyclopropyl]-2-hydroxybenzoic acid

6-[(1-{(2R)-2-amino-3-[(2-aminoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic acid

6-[(1-{(2S)-2-amino-3-[(2-aminoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic acid

6-[(1-{(2R)-2-amino-3-[(2-aminoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic acid

6-[(1-{(2S)-2-amino-3-[(2-aminoethyl)amino]-2-methyl-3-oxopropyl}azetidin-3-yl)oxy]-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic acid

3-(2-boronocyclopropyl)-6-[(1-histidylazetidin-3-yl)oxy]-2-hydroxybenzoic acid

3-[(1R,2S)-2-boronocyclopropyl]-6-[(1-D-histidylazetidin-3-yl)oxy]-2-hydroxybenzoic acid

3-[(1R,2S)-2-boronocyclopropyl]-6-[(1-L-histidylazetidin-3-yl)oxy]-2-hydroxybenzoic acid

3-[(1S,2R)-2-boronocyclopropyl]-6-[(1-D-histidylazetidin-3-yl)oxy]-2-hydroxybenzoic acid

3-[(1S,2R)-2-boronocyclopropyl]-6-[(1-L-histidylazetidin-3-yl)oxy]-2-hydroxybenzoic acid

6-{[1-(2-aminoethyl)azetidin-3-yl]oxy}-3-(2-boronocyclopropyl)-2-hydroxybenzoic acid

6-{[1-(2-aminoethyl)azetidin-3-yl]oxy}-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic acid

6-{[1-(2-aminoethyl)azetidin-3-yl]oxy}-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic acid

6-[(1-{[5-(aminomethyl)morpholin-2-yl]acetyl}azetidin-3-yl)oxy]-3-(2-boronocyclopropyl)-2-hydroxybenzoic acid

6-[(1-{[5-(aminomethyl)morpholin-2-yl]acetyl}azetidin-3-yl)oxy]-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic acid

6-[(1-{[5-(aminomethyl)morpholin-2-yl]acetyl}azetidin-3-yl)oxy]-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic acid

6-({1-[2-amino-2-methyl-3-{[2-(methylamino)-2-oxoethyl]amino}-3-oxopropyl]azetidin-3-yl}oxy)-3-[2-boronocyclopropyl]-2-hydroxybenzoic acid

6-({1-[(2R)-2-amino-2-methyl-3-{[2-(methylamino)-2-oxoethyl]amino}-3-oxopropyl]azetidin-3-yl}oxy)-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic acid

6-({1-[(2S)-2-amino-2-methyl-3-{[2-(methylamino)-2-oxoethyl]amino}-3-oxopropyl]azetidin-3-yl}oxy)-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic acid

6-({1-[(2R)-2-amino-2-methyl-3-{[2-(methylamino)-2-oxoethyl]amino}-3-oxopropyl]azetidin-3-yl}oxy)-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic acid

6-({1-[(2S)-2-amino-2-methyl-3-{[2-(methylamino)-2-oxoethyl]amino}-3-oxopropyl]azetidin-3-yl}oxy)-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic acid

6-({1-[2-amino-3-{[2-(dimethylamino)-2-oxoethyl]amino}-2-methyl-3-oxopropyl]azetidin-3-yl}oxy)-3-[2-boronocyclopropyl]-2-hydroxybenzoic acid

6-({1-[(2R)-2-amino-3-{[2-(dimethylamino)-2-oxoethyl]amino}-2-methyl-3-oxopropyl]azetidin-3-yl}oxy)-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic acid

6-({1-[(2S)-2-amino-3-{[2-(dimethylamino)-2-oxoethyl]amino}-2-methyl-3-oxopropyl]azetidin-3-yl}oxy)-3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxybenzoic acid

6-({1-[(2R)-2-amino-3-{[2-(dimethylamino)-2-oxoethyl]amino}-2-methyl-3-oxopropyl]azetidin-3-yl}oxy)-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic acid

6-({1-[(2S)-2-amino-3-{[2-(dimethylamino)-2-oxoethyl]amino}-2-methyl-3-oxopropyl]azetidin-3-yl}oxy)-3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxybenzoic acid

3-[2-boronocyclopropyl]-2-hydroxy-6-[(1-{[4-methylmorpholin-2-yl]acetyl}azetidin-3-yl)oxy]benzoic acid

3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxy-6-[(1-{[(2R)-4-methylmorpholin-2-yl]acetyl}azetidin-3-yl)oxy]benzoic acid

3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxy-6-[(1-{[(2S)-4-methylmorpholin-2-yl]acetyl}azetidin-3-yl)oxy]benzoic acid

3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxy-6-[(1-{[(2R)-4-methylmorpholin-2-yl]acetyl}azetidin-3-yl)oxy]benzoic acid

3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxy-6-[(1-{[(2S)-4-methylmorpholin-2-yl]acetyl}azetidin-3-yl)oxy]benzoic acid

3-[2-boronocyclopropyl]-6-[(1-{[4,4-dimethylmorpholin-4-ium-2-yl]acetyl}azetidin-3-yl)oxy]-2-hydroxybenzoate

3-[(1R,2S)-2-boronocyclopropyl]-6-[(1-{[(2R)-4,4-dimethylmorpholin-4-ium-2-yl]acetyl}azetidin-3-yl)oxy]-2-hydroxybenzoate

3-[(1R,2S)-2-boronocyclopropyl]-6-[(1-{[(2S)-4,4-dimethylmorpholin-4-ium-2-yl]acetyl}azetidin-3-yl)oxy]-2-hydroxybenzoate

3-[(1S,2R)-2-boronocyclopropyl]-6-[(1-{[(2R)-4,4-dimethylmorpholin-4-ium-2-yl]acetyl}azetidin-3-yl)oxy]-2-hydroxybenzoate

3-[(1S,2R)-2-boronocyclopropyl]-6-[(1-{[(2S)-4,4-dimethylmorpholin-4-ium-2-yl]acetyl}azetidin-3-yl)oxy]-2-hydroxybenzoate

3-(2-boronocyclopropyl)-2-hydroxy-6-({1-[(3-hydroxy-2-methyl-4-oxopyridin-1(4H)-yl)acetyl]azetidin-3-yl}oxy)benzoic acid

3-[(1S,2R)-2-boronocyclopropyl]-2-hydroxy-6-({1-[(3-hydroxy-2-methyl-4-oxopyridin-1(4H)-yl)acetyl]azetidin-3-yl}oxy)benzoic acid

and 3-[(1R,2S)-2-boronocyclopropyl]-2-hydroxy-6-({1-[(3-hydroxy-2-methyl-4-oxopyridin-1(4H)-yl)acetyl]azetidin-3-yl}oxy)benzoic acid


119. A medicament comprising the compound or the pharmaceutically acceptable salt thereof according to any one of claim 1 to claim
 118. 120. The medicament according to claim 119, which is a therapeutic drug or a prophylactic drug for a bacterial infection.
 121. An agent for inhibiting β-lactamase, comprising the compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 118 as an active ingredient.
 122. A pharmaceutical composition comprising the compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 118 and a pharmaceutically acceptable carrier.
 123. The pharmaceutical composition according to claim 122, further comprising an additional agent.
 124. The pharmaceutical composition according to claim 123, wherein the additional agent is selected from the group consisting of an antibacterial agent, an antifungal agent, an antiviral agent, an anti-inflammatory agent, and an anti-allergic agent.
 125. The pharmaceutical composition according to claim 123 or 124, wherein the additional agent is a β-lactam agent.
 126. The pharmaceutical composition according to claim 124 or 125, wherein a β-lactam agent, which is the additional agent, is selected from the group consisting of amoxicillin, ampicillin (pivampicillin, hetacillin, bacampicillin, metampicillin, and talampicillin), epicillin, carbenicillin (carindacillin), ticarcillin, temocillin, azlocillin, piperacillin, mezlocillin, mecillinam (pivmecillinam), sulbenicillin, benzylpenicillin (G), clometocillin, benzathine benzylpenicillin, procaine benzylpenicillin, azidocillin, penamecillin, phenoxymethyl penicillin (V), propicillin, benzathine phenoxymethylpenicillin, phenethicillin, cloxacillin (dicloxacillin and flucloxacillin), oxacillin, methicillin, nafcillin, faropenem, biapenem, doripenem, ertapenem, imipenem, meropenem, panipenem, tomopenem, razupenem, cefazolin, cefacetrile, cefadroxil, cephalexin, cefaloglycin, cefalonium, cefaloridine, cephalothin, cephapirin, cefatrizine, cefazedone, cefazaflur, cefradine, cefroxadine, ceftezole, cefaclor, cefamandole, cefminox, cefonicide, ceforanide, cefotiam, cefprozil, cefbuperazone, cefuroxime, cefuzonam, cefoxitin, cefotetan, cefmetazole, loracarbef, cefixime, ceftazidime, ceftriaxone, cefcapene, cefdaloxime, cefdinir, cefditoren, cefetamet, cefmenoxime, cefodizime, cefoperazone, cefotaxime, cefpimizole, cefpiramide, cefpodoxime, cefsulodin, cefteram, ceftibuten, ceftiolene, ceftizoxime, flomoxef, latamoxef, cefepime, cefozopran, cefpirome, cefquinome, ceftobiprole, ceftaroline, CXA-101, RWJ-54428, MC-04546, ME1036, BAL30072, SYN2416, ceftiofur, cefquinome, cefovecin, aztreonam, tigemonam, carumonam, RWJ-442831, RWJ-333441, and RWJ-333442.
 127. The pharmaceutical composition according to claim 125 or 126, wherein the β-lactam agent is selected from ceftazidime, biapenem, doripenem, ertapenem, imipenem, meropenem, or panipenem.
 128. The pharmaceutical composition according to claim 125 or 126, wherein the β-lactam agent is selected from aztreonam, tigemonam, BAL30072, SYN2416, or carumonam.
 129. The pharmaceutical composition according to claim 122, characterized in that an additional agent is concomitantly administered.
 130. The pharmaceutical composition according to claim 129, wherein the additional agent is selected from an antibacterial agent, an antifungal agent, an antiviral agent, an anti-inflammatory agent, or an anti-allergic agent.
 131. The pharmaceutical composition according to claim 129 or 130, wherein the additional agent is a β-lactam agent.
 132. The pharmaceutical composition according to claim 130 or 131, wherein a β-lactam agent, which is the additional agent, is selected from the group consisting of amoxicillin, ampicillin (pivampicillin, hetacillin, bacampicillin, metampicillin, and talampicillin), epicillin, carbenicillin (carindacillin), ticarcillin, temocillin, azlocillin, piperacillin, mezlocillin, mecillinam (pivmecillinam), sulbenicillin, benzylpenicillin (G), clometocillin, benzathine benzylpenicillin, procaine benzylpenicillin, azidocillin, penamecillin, phenoxymethyl penicillin (V), propicillin, benzathine phenoxymethylpenicillin, phenethicillin, cloxacillin (dicloxacillin and flucloxacillin), oxacillin, methicillin, nafcillin, faropenem, biapenem, doripenem, ertapenem, imipenem, meropenem, panipenem, tomopenem, razupenem, cefazolin, cefacetrile, cefadroxil, cephalexin, cefaloglycin, cefalonium, cefaloridine, cephalothin, cephapirin, cefatrizine, cefazedone, cefazaflur, cefradine, cefroxadine, ceftezole, cefaclor, cefamandole, cefminox, cefonicide, ceforanide, cefotiam, cefprozil, cefbuperazone, cefuroxime, cefuzonam, cefoxitin, cefotetan, cefmetazole, loracarbef, cefixime, ceftazidime, ceftriaxone, cefcapene, cefdaloxime, cefdinir, cefditoren, cefetamet, cefmenoxime, cefodizime, cefoperazone, cefotaxime, cefpimizole, cefpiramide, cefpodoxime, cefsulodin, cefteram, ceftibuten, ceftiolene, ceftizoxime, flomoxef, latamoxef, cefepime, cefozopran, cefpirome, cefquinome, ceftobiprole, ceftaroline, CXA-101, RWJ-54428, MC-04546, ME1036, BAL30072, SYN2416, ceftiofur, cefquinome, cefovecin, aztreonam, tigemonam, carumonam, RWJ-442831, RWJ-333441, and RWJ-333442.
 133. The pharmaceutical composition according to claim 131 or 132, wherein the β-lactam agent is selected from the group consisting of ceftazidime, biapenem, doripenem, ertapenem, imipenem, meropenem, and panipenem.
 134. The pharmaceutical composition according to claim 131 or 132, wherein the β-lactam agent is selected from the group consisting of aztreonam, tigemonam, BAL30072, SYN2416, and carumonam.
 135. The compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 118 for use in treating a bacterial infection.
 136. The compound or the pharmaceutically acceptable salt thereof according to claim 135, wherein the bacterial infection is a bacterial infection in which a bacteria that can have a (3-lactamase is involved.
 137. The compound or the pharmaceutically acceptable salt thereof according to claim 135 or 136, wherein the bacterial infection is sepsis, febrile neutropenia, bacterial meningitis, bacterial endocarditis, otitis media, sinusitis, pneumonia, lung abscess, empyema, secondary infection of a chronic respiratory disease, pharyngolaryngitis, tonsillitis, osteomyelitis, arthritis, peritonitis, intraperitoneal abscess, cholecystitis, cholangitis, liver abscess, a deep skin infection, lymphangitis/lymphadenitis, secondary infection of trauma, burn injury, surgical wound, or the like, a urinary tract infection, a genital infection, an eye infection, or an odontogenic infection.
 138. A medicament comprised of a combination of the compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 118 and at least one agent selected from the group consisting of therapeutic agents for sepsis, febrile neutropenia, bacterial meningitis, bacterial endocarditis, otitis media, sinusitis, pneumonia, lung abscess, empyema, secondary infection of a chronic respiratory disease, pharyngolaryngitis, tonsillitis, osteomyelitis, arthritis, peritonitis, intraperitoneal abscess, cholecystitis, cholangitis, liver abscess, a deep skin infection, lymphangitis/lymphadenitis, secondary infection of trauma, burn injury, surgical wound, or the like, a urinary tract infection, a genital infection, an eye infection, and an odontogenic infection.
 139. A pharmaceutical composition comprising a β-lactam agent, wherein the pharmaceutical composition is administered with the compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to
 118. 140. A method for treating a bacterial infection, characterized in that a therapeutically effective amount of the compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 118 is administered to a patient in need thereof.
 141. The method according to claim 140, wherein the bacterial infection is a bacterial infection in which a bacteria that can have a β-lactamase is involved.
 142. The method according to claim 140 or 141, wherein the bacterial infection is sepsis, febrile neutropenia, bacterial meningitis, bacterial endocarditis, otitis media, sinusitis, pneumonia, lung abscess, empyema, secondary infection of a chronic respiratory disease, pharyngolaryngitis, tonsillitis, osteomyelitis, arthritis, peritonitis, intraperitoneal abscess, cholecystitis, cholangitis, liver abscess, a deep skin infection, lymphangitis/lymphadenitis, secondary infection of trauma, burn injury, surgical wound, or the like, a urinary tract infection, a genital infection, an eye infection, or an odontogenic infection.
 143. The method according to any one of claims 140 to 142, characterized in that an additional agent is concomitantly administered. 